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Mendeliome v0.9385 MAGEL2 Zornitza Stark Mode of inheritance for gene: MAGEL2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Mendeliome v0.9384 MAGEL2 Zornitza Stark reviewed gene: MAGEL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24076603, 31397880, 29599419, 30302899; Phenotypes: Schaaf-Yang syndrome, MIM# 615547; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Imprinting disorders v0.33 MAGEL2 Zornitza Stark Marked gene: MAGEL2 as ready
Imprinting disorders v0.33 MAGEL2 Zornitza Stark Gene: magel2 has been classified as Green List (High Evidence).
Imprinting disorders v0.33 MAGEL2 Zornitza Stark Phenotypes for gene: MAGEL2 were changed from Schaaf-Yang syndrome; Chitayat-Hall Syndrome to Schaaf-Yang syndrome, MIM# 615547; Chitayat-Hall Syndrome
Imprinting disorders v0.32 MAGEL2 Zornitza Stark Classified gene: MAGEL2 as Green List (high evidence)
Imprinting disorders v0.32 MAGEL2 Zornitza Stark Gene: magel2 has been classified as Green List (High Evidence).
Imprinting disorders v0.31 MAGEL2 Zornitza Stark reviewed gene: MAGEL2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Schaaf-Yang syndrome, MIM# 615547; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Imprinting disorders v0.31 KCNQ1 Zornitza Stark Marked gene: KCNQ1 as ready
Imprinting disorders v0.31 KCNQ1 Zornitza Stark Gene: kcnq1 has been classified as Amber List (Moderate Evidence).
Imprinting disorders v0.31 KCNQ1 Zornitza Stark Publications for gene: KCNQ1 were set to PMID 30635621; 32393365; 30778172
Imprinting disorders v0.30 KCNQ1 Zornitza Stark Classified gene: KCNQ1 as Amber List (moderate evidence)
Imprinting disorders v0.30 KCNQ1 Zornitza Stark Gene: kcnq1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9384 L3MBTL1 Zornitza Stark Marked gene: L3MBTL1 as ready
Mendeliome v0.9384 L3MBTL1 Zornitza Stark Gene: l3mbtl1 has been classified as Red List (Low Evidence).
Mendeliome v0.9384 L3MBTL1 Zornitza Stark gene: L3MBTL1 was added
gene: L3MBTL1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: L3MBTL1 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for gene: L3MBTL1 were set to 23543057; 15123827; 30794780
Phenotypes for gene: L3MBTL1 were set to Affected tissue: myeloid lineages; Phenotype resulting from under expression: lymphoid malignancy
Review for gene: L3MBTL1 was set to RED
Added comment: Germline variation in this imprinted gene is not currently associated with disease.

Somatic deletions of 20q are associated with chronic myeloid malignancies. Aziz et al showed that a single heterozygous 20q deletion consistently resulted in the complete loss of expression of the imprinted genes L3MBTL1 and SGK2, indicative of a pathogenetic role for loss of the active paternally inherited locus. Concomitant loss of both L3MBTL1 and SGK2 dysregulated erythropoiesis and megakaryopoiesis.
Sources: Expert Review
Mendeliome v0.9383 KCNQ1OT1 Zornitza Stark Marked gene: KCNQ1OT1 as ready
Mendeliome v0.9383 KCNQ1OT1 Zornitza Stark Gene: kcnq1ot1 has been classified as Red List (Low Evidence).
Imprinting disorders v0.29 L3MBTL1 Zornitza Stark Marked gene: L3MBTL1 as ready
Imprinting disorders v0.29 L3MBTL1 Zornitza Stark Gene: l3mbtl1 has been classified as Red List (Low Evidence).
Imprinting disorders v0.29 L3MBTL1 Zornitza Stark Publications for gene: L3MBTL1 were set to http://igc.otago.ac.nz/home.html; 23543057; PMID: 15123827; 30794780
Imprinting disorders v0.28 L3MBTL1 Zornitza Stark Classified gene: L3MBTL1 as Red List (low evidence)
Imprinting disorders v0.28 L3MBTL1 Zornitza Stark Gene: l3mbtl1 has been classified as Red List (Low Evidence).
Mendeliome v0.9383 KCNQ1OT1 Zornitza Stark gene: KCNQ1OT1 was added
gene: KCNQ1OT1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: KCNQ1OT1 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for gene: KCNQ1OT1 were set to 22205991; 15372379; 23511928; 30794780; 29377879; 10220444; 32447323; 33177595; 29047350
Phenotypes for gene: KCNQ1OT1 were set to Beckwith-Wiedemann syndrome OMIM:130650; Russell-Silver Syndrome
Review for gene: KCNQ1OT1 was set to AMBER
Added comment: Limited evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype.

KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. IC2 is located within KCNQ1 intron 10. KCNQ1OT1 is maternally imprinted and paternally expressed. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the BWS patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C (PMID 30635621). Expression is increased in BWS due to IC2 epimutations or paternal UPD.

Single nucleotide variants within KCNQ1OT1 have not been definitively associated with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350).

Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation.

Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LoF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172).
Sources: Expert Review
Imprinting disorders v0.27 KCNQ1OT1 Zornitza Stark Publications for gene: KCNQ1OT1 were set to 22205991; 15372379; 23511928; 30794780; 29377879; 10220444; 32447323; 33177595; 29047350
Imprinting disorders v0.26 KCNQ1OT1 Zornitza Stark Marked gene: KCNQ1OT1 as ready
Imprinting disorders v0.26 KCNQ1OT1 Zornitza Stark Gene: kcnq1ot1 has been classified as Amber List (Moderate Evidence).
Imprinting disorders v0.26 KCNQ1OT1 Zornitza Stark Phenotypes for gene: KCNQ1OT1 were changed from Beckwith-Wiedemann syndrome OMIM:130650 to Beckwith-Wiedemann syndrome OMIM:130650; Russell-Silver Syndrome
Imprinting disorders v0.25 KCNQ1OT1 Zornitza Stark Publications for gene: KCNQ1OT1 were set to 22205991; 15372379; 10220444; http://igc.otago.ac.nz/home.html; 23511928; 30794780
Imprinting disorders v0.24 KCNQ1OT1 Zornitza Stark Classified gene: KCNQ1OT1 as Amber List (moderate evidence)
Imprinting disorders v0.24 KCNQ1OT1 Zornitza Stark Gene: kcnq1ot1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9382 H19 Zornitza Stark Marked gene: H19 as ready
Mendeliome v0.9382 H19 Zornitza Stark Gene: h19 has been classified as Red List (Low Evidence).
Mendeliome v0.9382 H19 Zornitza Stark gene: H19 was added
gene: H19 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: H19 was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene: H19 were set to 20007505; 15743916; 23118352; 21863054; 21571108; 18245780; 24916376; 25943194
Phenotypes for gene: H19 were set to Phenotypes resulting from gene over expression: Silver-Russell Syndrome (proven effects of dosage alteration rather than gene muation); Affected tissue: all; Phenotype resulting from under expression: Beckwith-Wiedemann Syndrome
Review for gene: H19 was set to RED
Added comment: Methylation changes rather than sequence variation are associated with BWS/RSS.
Sources: Expert Review
Additional findings_Paediatric v0.258 H19 Zornitza Stark Marked gene: H19 as ready
Additional findings_Paediatric v0.258 H19 Zornitza Stark Gene: h19 has been classified as Red List (Low Evidence).
Additional findings_Paediatric v0.258 H19 Zornitza Stark Classified gene: H19 as Red List (low evidence)
Additional findings_Paediatric v0.258 H19 Zornitza Stark Gene: h19 has been classified as Red List (Low Evidence).
Additional findings_Paediatric v0.257 H19 Zornitza Stark reviewed gene: H19: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Imprinting disorders v0.23 H19 Zornitza Stark Marked gene: H19 as ready
Imprinting disorders v0.23 H19 Zornitza Stark Gene: h19 has been classified as Red List (Low Evidence).
Imprinting disorders v0.23 H19 Zornitza Stark Classified gene: H19 as Red List (low evidence)
Imprinting disorders v0.23 H19 Zornitza Stark Gene: h19 has been classified as Red List (Low Evidence).
Imprinting disorders v0.22 H19 Zornitza Stark reviewed gene: H19: Rating: RED; Mode of pathogenicity: None; Publications: 20007505, 15743916, 23118352, 21863054, 21571108, 18245780, 24916376, 25943194; Phenotypes: Phenotypes resulting from gene over expression: Silver-Russell Syndrome (proven effects of dosage alteration rather than gene muation), Affected tissue: all, Phenotype resulting from under expression: Beckwith-Wiedemann Syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Imprinting disorders v0.22 GNAS Zornitza Stark Marked gene: GNAS as ready
Imprinting disorders v0.22 GNAS Zornitza Stark Gene: gnas has been classified as Green List (High Evidence).
Imprinting disorders v0.22 GNAS Zornitza Stark Phenotypes for gene: GNAS were changed from Affected tissue: kidney, bone, brain; pseudopseudohypoparathyroidism; Phenotype resulting from under expression: Pseudohypoparathyroidism Type 1a to Affected tissue: kidney, bone, brain; pseudopseudohypoparathyroidism; Phenotype resulting from under expression: Pseudohypoparathyroidism Type 1a, MIM# 103580; Albright hereditary osteodystrophy
Imprinting disorders v0.21 GNAS Zornitza Stark Publications for gene: GNAS were set to 10980525; 11406605; 12024005; 15800843; 15181091; 9506752; 12024004; 15592469; 15592469; 11788646; 1944469; 2109828; 30794780
Imprinting disorders v0.20 GNAS Zornitza Stark Publications for gene: GNAS were set to 10980525; [11406605; 12024005; 15800843]; 15181091; 9506752; 12024004; http://igc.otago.ac.nz/home.html; 15592469; [15592469; 11788646; 1944469; PMID: 2109828; 30794780
Imprinting disorders v0.19 GNAS Zornitza Stark edited their review of gene: GNAS: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Imprinting disorders v0.19 GNAS Zornitza Stark reviewed gene: GNAS: Rating: GREEN; Mode of pathogenicity: None; Publications: 15331575; Phenotypes: Pseudohypoparathyroidism Ia, MIM# 103580, Albright hereditary osteodystrophy, Pseudohypoparathyroidism Ib, MIM# 603233; Mode of inheritance: None
Mendeliome v0.9381 GBF1 Zornitza Stark Phenotypes for gene: GBF1 were changed from Axonal Neuropathy to Charcot-Marie-Tooth disease, dominant intermediate A, MIM# 606483; Axonal Neuropathy
Mendeliome v0.9380 GBF1 Zornitza Stark reviewed gene: GBF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, dominant intermediate A, MIM# 606483; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Syndromic Retinopathy v0.179 TMEM218 Zornitza Stark Phenotypes for gene: TMEM218 were changed from Joubert syndrome; retinal dystrophy; polycystic kidneys; occipital encephalocele to Joubert syndrome 39, MIM#619562; retinal dystrophy; polycystic kidneys; occipital encephalocele
Syndromic Retinopathy v0.178 TMEM218 Zornitza Stark reviewed gene: TMEM218: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Joubert syndrome 39, MIM#619562; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9380 TMEM218 Zornitza Stark Phenotypes for gene: TMEM218 were changed from Joubert syndrome; retinal dystrophy; polycystic kidneys; occipital encephalocele to Joubert syndrome 39, MIM#619562; retinal dystrophy; polycystic kidneys; occipital encephalocele
Mendeliome v0.9379 TMEM218 Zornitza Stark reviewed gene: TMEM218: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Joubert syndrome 39, MIM#619562; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v1.15 TMEM218 Zornitza Stark Phenotypes for gene: TMEM218 were changed from Joubert syndrome; retinal dystrophy; polycystic kidneys; occipital encephalocele to Joubert syndrome 39, MIM#619562; retinal dystrophy; polycystic kidneys; occipital encephalocele
Joubert syndrome and other neurological ciliopathies v1.14 TMEM218 Zornitza Stark reviewed gene: TMEM218: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Joubert syndrome 39, MIM#619562; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Imprinting disorders v0.19 MAGEL2 Anna Le Fevre changed review comment from: MAGEL2 is a single-exon gene.
Frameshift mutations may not cause nonsense-mediated decay, but instead a variety of truncated or elongated protein products.
The pathogenicity of haploinsufficiency of the paternal allele is uncertain (ClinGen review 2018). A dominant-negative effect has been suggested. Haploinsufficiency may play a role.
Sources: Literature; to: Multiple reports.

MAGEL2 is a single-exon gene.
Frameshift mutations may not cause nonsense-mediated decay, but instead a variety of truncated or elongated protein products.
The pathogenicity of haploinsufficiency of the paternal allele is uncertain (ClinGen review 2018). A dominant-negative effect has been suggested. Haploinsufficiency may play a role.
Sources: Literature
Mendeliome v0.9379 OOEP Zornitza Stark Marked gene: OOEP as ready
Mendeliome v0.9379 OOEP Zornitza Stark Gene: ooep has been classified as Red List (Low Evidence).
Mendeliome v0.9379 OOEP Zornitza Stark gene: OOEP was added
gene: OOEP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: OOEP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OOEP were set to 29574422
Phenotypes for gene: OOEP were set to Multi locus imprinting disturbance in offspring
Review for gene: OOEP was set to RED
Added comment: Single report of biallelic variants in this gene in a mother of a child with Multi locus imprinting disturbance (MLID) and a transient neonatal diabetes mellitus phenotype.

This gene encodes part of the subcortical maternal complex (SCMC). Other genes in this group act as 'maternal effect' genes and are associated with early embryonic arrest, recurrent hydatiform mole and MLID in offspring.

As is the case for other genes encoding components of the SCMC, the pathogenicity of variants can be difficult to establish as reproductive outcomes are not recorded in genomic databases and variants may be listed in population databases as they are not classed as pathogenic in males or women with no reproductive history.

Functional studies of genes encoding components of the SCMC are limited as their expression is restricted to the oocyte and early embryo.
Sources: Literature
Imprinting disorders v0.19 OOEP Zornitza Stark Marked gene: OOEP as ready
Imprinting disorders v0.19 OOEP Zornitza Stark Gene: ooep has been classified as Red List (Low Evidence).
Imprinting disorders v0.19 OOEP Zornitza Stark Classified gene: OOEP as Red List (low evidence)
Imprinting disorders v0.19 OOEP Zornitza Stark Gene: ooep has been classified as Red List (Low Evidence).
Imprinting disorders v0.18 OOEP Zornitza Stark reviewed gene: OOEP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.9378 ZNF445 Zornitza Stark Marked gene: ZNF445 as ready
Mendeliome v0.9378 ZNF445 Zornitza Stark Gene: znf445 has been classified as Red List (Low Evidence).
Mendeliome v0.9378 ZNF445 Zornitza Stark gene: ZNF445 was added
gene: ZNF445 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZNF445 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF445 were set to 34039421; 30602440; 30846001
Phenotypes for gene: ZNF445 were set to Temple syndrome; Multi locus imprinting disturbance (MLID)
Review for gene: ZNF445 was set to RED
Added comment: Single report (Kagami 2021) of a child with Temple syndrome and MLID found to have a novel homozygous truncating variant in ZNF445.

ZNF445 has been shown to play a critical role in the maintenance of postfertilisation methylation imprints (Takahashi 2019). Mechanism and parent of origin effects remain uncertain.
Sources: Literature
Imprinting disorders v0.18 ZNF445 Zornitza Stark Marked gene: ZNF445 as ready
Imprinting disorders v0.18 ZNF445 Zornitza Stark Gene: znf445 has been classified as Red List (Low Evidence).
Imprinting disorders v0.18 ZNF445 Zornitza Stark Classified gene: ZNF445 as Red List (low evidence)
Imprinting disorders v0.18 ZNF445 Zornitza Stark Gene: znf445 has been classified as Red List (Low Evidence).
Imprinting disorders v0.17 ZNF445 Zornitza Stark reviewed gene: ZNF445: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Imprinting disorders v0.17 TLE6 Zornitza Stark Marked gene: TLE6 as ready
Imprinting disorders v0.17 TLE6 Zornitza Stark Gene: tle6 has been classified as Amber List (Moderate Evidence).
Imprinting disorders v0.17 TLE6 Zornitza Stark Classified gene: TLE6 as Amber List (moderate evidence)
Imprinting disorders v0.17 TLE6 Zornitza Stark Gene: tle6 has been classified as Amber List (Moderate Evidence).
Imprinting disorders v0.16 NLRP7 Zornitza Stark Publications for gene: NLRP7 were set to 19246479; 28916717; 31201414; 16462743; 29574422
Imprinting disorders v0.15 KHDC3L Zornitza Stark Marked gene: KHDC3L as ready
Imprinting disorders v0.15 KHDC3L Zornitza Stark Gene: khdc3l has been classified as Green List (High Evidence).
Imprinting disorders v0.15 KHDC3L Zornitza Stark Phenotypes for gene: KHDC3L were changed from Hydatiform mold recurrent 2 MIM#614293 to Hydatiform mole recurrent 2 MIM#614293
Imprinting disorders v0.14 KHDC3L Zornitza Stark Classified gene: KHDC3L as Green List (high evidence)
Imprinting disorders v0.14 KHDC3L Zornitza Stark Gene: khdc3l has been classified as Green List (High Evidence).
Imprinting disorders v0.13 KCNQ1 Anna Le Fevre changed review comment from: Proposed classification: Amber, pending further evidence.

The KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5 is located within KCNQ1 intron 10.

IC2 corresponds to the promoter of the long noncoding RNA KCNQ1OT1 and is methylated and inactive on the maternal chromosome. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the Beckwith-Wiedemann Syndrome (BWS) patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C (PMID 30635621).

Pathogenic variants in KCNQ1 are associated with long-QT syndrome (LQTS) and can be inherited on the paternal or maternal allele.

Loss of methylation (LOM) of IC2 has been reported in a small number of individuals with KCNQ1 germline variants which additionally cause LQTS. Valente et al (PMID 30635621) reported three individuals with LQTS, features of BWS and LOM at IC2 and maternally inherited KCNQ1 variants, two of which were demonstrated to affect KCNQ1 transcription upstream of IC2. Essinger et al (PMID 32393365) analysed KCNQ1 in 52 individuals with LOM at IC2 and identified one individual with a splice site variant causing premature transcription termination.

Microdeletions of IC2 variably involving KCNQ1, CDKN1C and KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. LoF in CDKN1C is a known cause of BWS.

Beygo et al (PMID 30778172) demonstrated that disruption of KCNQ1 prevents methylation of IC2 supporting the hypothesis that transcription of KCNQ1 is required for establishing the maternal methylation imprint at IC2.
Sources: Literature; to: Proposed classification: Amber, pending further evidence.

The KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5 is located within KCNQ1 intron 10.

IC2 corresponds to the promoter of the long noncoding RNA KCNQ1OT1 and is methylated and inactive on the maternal chromosome. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the Beckwith-Wiedemann Syndrome (BWS) patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C (PMID 30635621).

Pathogenic variants in KCNQ1 are associated with long-QT syndrome (LQTS) and can be inherited on the paternal or maternal allele.

Loss of methylation (LOM) of IC2 has been reported in a small number of individuals with KCNQ1 germline variants which additionally cause LQTS. Valente et al (PMID 30635621) reported three individuals with LQTS, features of BWS and LOM at IC2 and maternally inherited KCNQ1 variants, two of which were demonstrated to affect KCNQ1 transcription upstream of IC2. Essinger et al (PMID 32393365) analysed KCNQ1 in 52 individuals with LOM at IC2 and identified one individual with a splice site variant causing premature transcription termination.

Microdeletions of IC2 variably involving KCNQ1, CDKN1C and KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. Maternally inherited LoF variants in CDKN1C are a known cause of BWS.

Beygo et al (PMID 30778172) demonstrated that disruption of KCNQ1 prevents methylation of IC2 supporting the hypothesis that transcription of KCNQ1 is required for establishing the maternal methylation imprint at IC2.
Sources: Literature
Imprinting disorders v0.13 KCNQ1OT1 Anna Le Fevre changed review comment from: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype.

KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. IC2 is located within KCNQ1 intron 10. KCNQ1OT1 is maternally imprinted and paternally expressed. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the BWS patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C (PMID 30635621).

Single nucleotide variants within KCNQ1OT1 have not been definitively associated with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350).

Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation.

Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LoF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172). ; to: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype.

KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. IC2 is located within KCNQ1 intron 10. KCNQ1OT1 is maternally imprinted and paternally expressed. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the BWS patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C (PMID 30635621). Expression is increased in BWS due to IC2 epimutations or paternal UPD.

Single nucleotide variants within KCNQ1OT1 have not been definitively associated with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350).

Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation.

Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LoF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172).
Imprinting disorders v0.13 KCNQ1OT1 Anna Le Fevre changed review comment from: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype.

KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. IC2 is located within KCNQ1 intron 10. KCNQ1OT1 is maternally imprinted and paternally expressed. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the BWS patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C.

Single nucleotide variants within KCNQ1OT1 have not been definitively associated with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350).

Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation.

Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LoF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172). ; to: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype.

KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. IC2 is located within KCNQ1 intron 10. KCNQ1OT1 is maternally imprinted and paternally expressed. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the BWS patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C (PMID 30635621).

Single nucleotide variants within KCNQ1OT1 have not been definitively associated with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350).

Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation.

Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LoF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172).
Imprinting disorders v0.13 KCNQ1OT1 Anna Le Fevre changed review comment from: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype.

KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. IC2 is located within KCNQ1 intron 10. KCNQ1OT1 is maternally imprinted and paternally expressed. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the BWS patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C.

Single nucleotide variants within KCNQ1OT1 have not been definitively association with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350).

Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation.

Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LoF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172). ; to: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype.

KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. IC2 is located within KCNQ1 intron 10. KCNQ1OT1 is maternally imprinted and paternally expressed. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the BWS patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C.

Single nucleotide variants within KCNQ1OT1 have not been definitively associated with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350).

Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation.

Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LoF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172).
Imprinting disorders v0.13 KCNQ1OT1 Anna Le Fevre changed review comment from: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype.

KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. KCNQ1OT1 is maternally imprinted and paternally expressed.

Single nucleotide variants within KCNQ1OT1 have not been definitively association with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350).

Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation.

Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LoF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172).

Genomic analysis of KCNQ1OT1 was not recommended as part of the diagnostic algorithm for suspected BWS in a 2018 international consensus review (PMID 29377879).; to: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype.

KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. IC2 is located within KCNQ1 intron 10. KCNQ1OT1 is maternally imprinted and paternally expressed. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the BWS patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C.

Single nucleotide variants within KCNQ1OT1 have not been definitively association with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350).

Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation.

Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LoF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172).
Imprinting disorders v0.13 KCNQ1 Anna Le Fevre gene: KCNQ1 was added
gene: KCNQ1 was added to Imprinting disorders. Sources: Literature
Mode of inheritance for gene: KCNQ1 was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene: KCNQ1 were set to PMID 30635621; 32393365; 30778172
Phenotypes for gene: KCNQ1 were set to Beckwith-Wiedemann Syndrome
Penetrance for gene: KCNQ1 were set to unknown
Review for gene: KCNQ1 was set to AMBER
Added comment: Proposed classification: Amber, pending further evidence.

The KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5 is located within KCNQ1 intron 10.

IC2 corresponds to the promoter of the long noncoding RNA KCNQ1OT1 and is methylated and inactive on the maternal chromosome. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the Beckwith-Wiedemann Syndrome (BWS) patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C (PMID 30635621).

Pathogenic variants in KCNQ1 are associated with long-QT syndrome (LQTS) and can be inherited on the paternal or maternal allele.

Loss of methylation (LOM) of IC2 has been reported in a small number of individuals with KCNQ1 germline variants which additionally cause LQTS. Valente et al (PMID 30635621) reported three individuals with LQTS, features of BWS and LOM at IC2 and maternally inherited KCNQ1 variants, two of which were demonstrated to affect KCNQ1 transcription upstream of IC2. Essinger et al (PMID 32393365) analysed KCNQ1 in 52 individuals with LOM at IC2 and identified one individual with a splice site variant causing premature transcription termination.

Microdeletions of IC2 variably involving KCNQ1, CDKN1C and KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. LoF in CDKN1C is a known cause of BWS.

Beygo et al (PMID 30778172) demonstrated that disruption of KCNQ1 prevents methylation of IC2 supporting the hypothesis that transcription of KCNQ1 is required for establishing the maternal methylation imprint at IC2.
Sources: Literature
Imprinting disorders v0.13 KCNQ1OT1 Anna Le Fevre changed review comment from: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype.

KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. KCNQ1OT1 is maternally imprinted and paternally expressed.

Single nucleotide variants within KCNQ1OT1 have not been definitively association with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350).

Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation.

Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LOF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172).

Genomic analysis of KCNQ1OT1 was not recommended as part of the diagnostic algorithm for suspected BWS in a 2018 international consensus review (PMID 29377879).; to: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype.

KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. KCNQ1OT1 is maternally imprinted and paternally expressed.

Single nucleotide variants within KCNQ1OT1 have not been definitively association with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350).

Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation.

Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LoF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172).

Genomic analysis of KCNQ1OT1 was not recommended as part of the diagnostic algorithm for suspected BWS in a 2018 international consensus review (PMID 29377879).
Imprinting disorders v0.13 KCNQ1OT1 Anna Le Fevre changed review comment from: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype.

KCNQ1OT1 encodes the regulatory non-coding RNA KCNQ1OT1 and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. KCNQ1OT1 is maternally imprinted and paternally expressed.

Single nucleotide variants within KCNQ1OT1 have not been definitively association with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350).

Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation.

Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involved neighboring genes KCNQ1 or CDKN1C. LOF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172).

Genomic analysis of KCNQ1OT1 was not recommended as part of the diagnostic algorithm for suspected BWS in a 2018 international consensus review (PMID 29377879).; to: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype.

KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. KCNQ1OT1 is maternally imprinted and paternally expressed.

Single nucleotide variants within KCNQ1OT1 have not been definitively association with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350).

Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation.

Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LOF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172).

Genomic analysis of KCNQ1OT1 was not recommended as part of the diagnostic algorithm for suspected BWS in a 2018 international consensus review (PMID 29377879).
Imprinting disorders v0.13 KCNQ1OT1 Anna Le Fevre reviewed gene: KCNQ1OT1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 29377879, 10220444, 32447323, 33177595, 29047350; Phenotypes: Growth restriction, Beckwith-Wiedemann Syndrome, Russell-Silver Syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Imprinting disorders v0.13 L3MBTL1 Anna Le Fevre reviewed gene: L3MBTL1: Rating: RED; Mode of pathogenicity: None; Publications: 23543057; Phenotypes: ; Mode of inheritance: None
Imprinting disorders v0.13 ZAR1 Anna Le Fevre gene: ZAR1 was added
gene: ZAR1 was added to Imprinting disorders. Sources: Literature
Mode of inheritance for gene: ZAR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZAR1 were set to 29574422; 31598710; 12539046
Phenotypes for gene: ZAR1 were set to Multi locus imprinting disturbance in offspring
Penetrance for gene: ZAR1 were set to unknown
Review for gene: ZAR1 was set to AMBER
Added comment: Proposed classification: Amber, pending further evidence.

Single report of biallelic variants in this gene in a mother of a child with Multi locus imprinting disturbance (MLID) with some features of Beckwith Wiedemann Syndrome.

Shown to be a maternal effect gene that functions at the oocyte to embryo transition.
Sources: Literature
Imprinting disorders v0.13 UHRF1 Anna Le Fevre gene: UHRF1 was added
gene: UHRF1 was added to Imprinting disorders. Sources: Literature
Mode of inheritance for gene: UHRF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UHRF1 were set to 29574422; 28976982
Phenotypes for gene: UHRF1 were set to Multi locus imprinting disturbance in offspring
Penetrance for gene: UHRF1 were set to unknown
Review for gene: UHRF1 was set to AMBER
Added comment: Proposed classification: Amber, pending further evidence.

Single report of biallelic variants in this gene in a mother of a child with Multi locus imprinting disturbance (MLID) and Silver Russell Syndrome phenotype.

Maenohara et al demonstrate functions of UHRF1 during the global epigenetic reprogramming of oocytes and early embryos.
Sources: Literature
Imprinting disorders v0.13 OOEP Anna Le Fevre gene: OOEP was added
gene: OOEP was added to Imprinting disorders. Sources: Literature
Mode of inheritance for gene: OOEP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OOEP were set to 29574422
Phenotypes for gene: OOEP were set to Multi locus imprinting disturbance in offspring
Penetrance for gene: OOEP were set to unknown
Review for gene: OOEP was set to AMBER
Added comment: Proposed classification: Amber, pending further evidence.

Single report of biallelic variants in this gene in a mother of a child with Multi locus imprinting disturbance (MLID) and a transient neonatal diabetes mellitus phenotype.

This gene encodes part of the subcortical maternal complex (SCMC). Other genes in this group act as 'maternal effect' genes and are associated with early embryonic arrest, recurrent hydatiform mole and MLID in offspring.

As is the case for other genes encoding components of the SCMC, the pathogenicity of variants can be difficult to establish as reproductive outcomes are not recorded in genomic databases and variants may be listed in population databases as they are not classed as pathogenic in males or women with no reproductive history.

Functional studies of genes encoding components of the SCMC are limited as their expression is restricted to the oocyte and early embryo.
Sources: Literature
Imprinting disorders v0.13 TLE6 Anna Le Fevre gene: TLE6 was added
gene: TLE6 was added to Imprinting disorders. Sources: Literature
Mode of inheritance for gene: TLE6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TLE6 were set to 26537248; 25542835
Phenotypes for gene: TLE6 were set to Pre-implantation embryonic lethality MIM#616814
Penetrance for gene: TLE6 were set to unknown
Review for gene: TLE6 was set to AMBER
Added comment: The first report of a single homozygous missense variant in three women from two families with primary infertility was published in 2015. In 2021, Zheng et al reported six biallelic variants in TLE6 in five patients with embryonic arrest, accompanied by direct cleavage and severe fragmentation at the cleavage stage. A mechanism is proposed.

I am uncertain regarding classification of this gene (amber vs green) due to the low specificity of this phenotype. I am uncertain if the changes seen in the early embryo, such as fragmentation, make this phenotype more specific.

As is the case for other genes encoding components of the subcortical maternal complex (SCMC), the pathogenicity of variants can be difficult to establish as reproductive outcomes are not recorded in genomic databases and variants may be listed in population databases as they are not classed as pathogenic in males or women with no reproductive history.

Functional studies of genes encoding components of the SCMC are limited as their expression is restricted to the oocyte and early embryo.
Sources: Literature
Imprinting disorders v0.13 NLRP7 Anna Le Fevre edited their review of gene: NLRP7: Added comment: There is one report of an individual with recurrent hydatiform mole and biallelic variants in this gene who experienced a single digynic triploid pregnancy presenting as a CHM, whereas other pregnancies were BiCHM (23125094).; Changed publications: 16462743, 28561018, 29574422, 19246479, 22315435, 19066229, 23722513, 23125094
Imprinting disorders v0.13 KHDC3L Anna Le Fevre gene: KHDC3L was added
gene: KHDC3L was added to Imprinting disorders. Sources: Literature
Mode of inheritance for gene: KHDC3L was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: KHDC3L were set to 23232697; 31847873; 23125094; 21885028
Phenotypes for gene: KHDC3L were set to Hydatiform mold recurrent 2 MIM#614293
Penetrance for gene: KHDC3L were set to unknown
Review for gene: KHDC3L was set to GREEN
Added comment: Biallelic pathogenic variants in the gene have been associated with Biparental complete hydatifom mole (BiCHM) in multiple individuals. There is one report of an individual with recurrent hydatiform mole and biallelic variants in this gene who experienced a single digynic triploid pregnancy presenting as a CHM, whereas other pregnancies were BiCHM (23125094).

Most reported individuals have been found to carry biallelic pathogenic variants in this gene. A minority have been found to carry a heterozygous variant only. A relationship between zygosity and severity of the condition has not been definitively established.

As is the case for other genes encoding components of the subcortical maternal complex (SCMC), the pathogenicity of variants can be difficult to establish as reproductive outcomes are not recorded in genomic databases and variants may be listed in population databases as they are not classed as pathogenic in males or women with no reproductive history.

Functional studies of genes encoding components of the SCMC are limited as their expression is restricted to the oocyte and early embryo.
Sources: Literature
Mendeliome v0.9377 NSRP1 Zornitza Stark Marked gene: NSRP1 as ready
Mendeliome v0.9377 NSRP1 Zornitza Stark Gene: nsrp1 has been classified as Green List (High Evidence).
Mendeliome v0.9377 NSRP1 Zornitza Stark Classified gene: NSRP1 as Green List (high evidence)
Mendeliome v0.9377 NSRP1 Zornitza Stark Gene: nsrp1 has been classified as Green List (High Evidence).
Mendeliome v0.9376 NSRP1 Zornitza Stark gene: NSRP1 was added
gene: NSRP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NSRP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NSRP1 were set to 34385670
Phenotypes for gene: NSRP1 were set to Epilepsy; Cerebral palsy; microcephaly; Intellectual disability
Review for gene: NSRP1 was set to GREEN
Added comment: Novel gene regulating splicing. Biallelic LoF pathogenic variants reported in 6 individuals from 3 unrelated families associated with a phenotype characterized by developmental delay, epilepsy, microcephaly, and spastic cerebral palsy.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4204 NSRP1 Zornitza Stark Marked gene: NSRP1 as ready
Intellectual disability syndromic and non-syndromic v0.4204 NSRP1 Zornitza Stark Gene: nsrp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4204 NSRP1 Zornitza Stark Classified gene: NSRP1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4204 NSRP1 Zornitza Stark Gene: nsrp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4203 NSRP1 Zornitza Stark reviewed gene: NSRP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.62 NSRP1 Zornitza Stark Marked gene: NSRP1 as ready
Microcephaly v1.62 NSRP1 Zornitza Stark Gene: nsrp1 has been classified as Green List (High Evidence).
Microcephaly v1.62 NSRP1 Zornitza Stark Classified gene: NSRP1 as Green List (high evidence)
Microcephaly v1.62 NSRP1 Zornitza Stark Gene: nsrp1 has been classified as Green List (High Evidence).
Microcephaly v1.61 NSRP1 Zornitza Stark reviewed gene: NSRP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.17 NSRP1 Zornitza Stark Marked gene: NSRP1 as ready
Cerebral Palsy v1.17 NSRP1 Zornitza Stark Gene: nsrp1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.17 NSRP1 Zornitza Stark Classified gene: NSRP1 as Green List (high evidence)
Cerebral Palsy v1.17 NSRP1 Zornitza Stark Gene: nsrp1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.16 NSRP1 Zornitza Stark reviewed gene: NSRP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1317 NSRP1 Zornitza Stark Marked gene: NSRP1 as ready
Genetic Epilepsy v0.1317 NSRP1 Zornitza Stark Gene: nsrp1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1317 NSRP1 Zornitza Stark Classified gene: NSRP1 as Green List (high evidence)
Genetic Epilepsy v0.1317 NSRP1 Zornitza Stark Gene: nsrp1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1316 NSRP1 Zornitza Stark reviewed gene: NSRP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Imprinting disorders v0.13 NLRP2 Zornitza Stark Marked gene: NLRP2 as ready
Imprinting disorders v0.13 NLRP2 Zornitza Stark Gene: nlrp2 has been classified as Green List (High Evidence).
Imprinting disorders v0.13 NLRP2 Zornitza Stark Phenotypes for gene: NLRP2 were changed from Beckwith-Wiedemann syndrome due to imprinting defect of 11p15 MONDO:0016475 to Beckwith-Wiedemann syndrome due to imprinting defect of 11p15 MONDO:0016475; Early embryonic arrest; Multi locus imprinting disturbance in offspring
Imprinting disorders v0.12 NLRP2 Zornitza Stark reviewed gene: NLRP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Imprinting disorders v0.12 PADI6 Zornitza Stark Marked gene: PADI6 as ready
Imprinting disorders v0.12 PADI6 Zornitza Stark Gene: padi6 has been classified as Green List (High Evidence).
Imprinting disorders v0.12 PADI6 Zornitza Stark Mode of inheritance for gene: PADI6 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Imprinting disorders v0.11 NLRP7 Zornitza Stark Marked gene: NLRP7 as ready
Imprinting disorders v0.11 NLRP7 Zornitza Stark Gene: nlrp7 has been classified as Green List (High Evidence).
Imprinting disorders v0.11 NLRP7 Zornitza Stark Mode of inheritance for gene: NLRP7 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9375 ERGIC1 Zornitza Stark Publications for gene: ERGIC1 were set to 28317099; 34037256
Mendeliome v0.9374 ERGIC1 Zornitza Stark Classified gene: ERGIC1 as Green List (high evidence)
Mendeliome v0.9374 ERGIC1 Zornitza Stark Gene: ergic1 has been classified as Green List (High Evidence).
Mendeliome v0.9373 ERGIC1 Zornitza Stark edited their review of gene: ERGIC1: Added comment: Pehlivan et al. 2019 (PMID:31230720) identified the third case of arthrogryposis in a child who harboured a previously unreported homozygous variant (c.782G>A; p.Gly261Asp) in this gene. Parents were heterozygous carriers. Functional studies were not performed.; Changed rating: GREEN; Changed publications: 28317099, 34037256, 31230720
Arthrogryposis v0.303 ERGIC1 Zornitza Stark Publications for gene: ERGIC1 were set to 28317099, 34037256; 31230720
Arthrogryposis v0.302 ERGIC1 Zornitza Stark Publications for gene: ERGIC1 were set to PMID: 28317099, 34037256
Arthrogryposis v0.301 ERGIC1 Zornitza Stark Classified gene: ERGIC1 as Green List (high evidence)
Arthrogryposis v0.301 ERGIC1 Zornitza Stark Gene: ergic1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4203 NSRP1 Krithika Murali gene: NSRP1 was added
gene: NSRP1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: NSRP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NSRP1 were set to 34385670
Phenotypes for gene: NSRP1 were set to Epilepsy; Cerebral palsy; microcephaly; Intellectual disability
Review for gene: NSRP1 was set to AMBER
Added comment: Novel gene regulating splicing. Biallelic LoF pathogenic variants reported in 6 individuals from 3 unrelated families associated with a phenotype characterized by developmental delay, epilepsy, microcephaly, and spastic cerebral palsy.
Sources: Literature
Microcephaly v1.61 NSRP1 Krithika Murali gene: NSRP1 was added
gene: NSRP1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: NSRP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NSRP1 were set to 34385670
Phenotypes for gene: NSRP1 were set to Epilepsy; Cerebral palsy; microcephaly; Intellectual disability
Review for gene: NSRP1 was set to AMBER
Added comment: Novel gene regulating splicing. Biallelic LoF pathogenic variants reported in 6 individuals from 3 unrelated families associated with a phenotype characterized by developmental delay, epilepsy, microcephaly, and spastic cerebral palsy.
Sources: Literature
Cerebral Palsy v1.16 NSRP1 Krithika Murali gene: NSRP1 was added
gene: NSRP1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NSRP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NSRP1 were set to 34385670
Phenotypes for gene: NSRP1 were set to Epilepsy; Cerebral palsy; microcephaly; Intellectual disability
Review for gene: NSRP1 was set to AMBER
Added comment: Novel gene regulating splicing. Biallelic LoF pathogenic variants reported in 6 individuals from 3 unrelated families associated with a phenotype characterized by developmental delay, epilepsy, microcephaly, and spastic cerebral palsy.
Sources: Literature
Genetic Epilepsy v0.1316 NSRP1 Krithika Murali gene: NSRP1 was added
gene: NSRP1 was added to Genetic Epilepsy. Sources: Expert list,Literature
Mode of inheritance for gene: NSRP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NSRP1 were set to 34385670
Phenotypes for gene: NSRP1 were set to Epilepsy; Cerebral palsy; microcephaly; Intellectual disability
Review for gene: NSRP1 was set to AMBER
Added comment: Novel gene regulating splicing. Biallelic LoF pathogenic variants reported in 6 individuals from 3 unrelated families associated with a phenotype characterized by developmental delay, epilepsy, microcephaly, and spastic cerebral palsy.
Sources: Expert list, Literature
Imprinting disorders v0.10 NLRP2 Anna Le Fevre reviewed gene: NLRP2: Rating: ; Mode of pathogenicity: None; Publications: PMID: 30877238, 28317850, 29574422; Phenotypes: Early embryonic arrest, Multi locus imprinting disturbance in offspring; Mode of inheritance: None
Imprinting disorders v0.10 PADI6 Anna Le Fevre reviewed gene: PADI6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29693651, 33583041, 329228291, 33221824, 27545678; Phenotypes: Pre-implantation embryonic lethality 2 MIM#617234, Multi locus imprinting disturbance in offspring, Recurrent hydatiform mole; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4203 GABRD Zornitza Stark Marked gene: GABRD as ready
Intellectual disability syndromic and non-syndromic v0.4203 GABRD Zornitza Stark Gene: gabrd has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4203 GABRD Zornitza Stark Classified gene: GABRD as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4203 GABRD Zornitza Stark Gene: gabrd has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4202 GABRD Zornitza Stark gene: GABRD was added
gene: GABRD was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: GABRD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABRD were set to 15115768; 34633442
Phenotypes for gene: GABRD were set to Intellectual disability; Epilepsy; Susceptibility to epilepsy, MIM#613060
Review for gene: GABRD was set to GREEN
Added comment: Susceptibility to epilepsy, MIM#613060: Limited reports. The variant originally reported in PMID 15115768 in association with epilepsy is present in >4,000 hets in gnomad and 55 homs which is not consistent with a Mendelian disorder.

PMID 34633442: 10 individuals with 7 unique variants reported in individuals with neurodevelopmental disorders and epilepsy. Six of the variants were demonstrated to be GoF, and those individuals with neurodevelopmental disorders with behavioural issues, various degrees of intellectual disability, generalized epilepsy with atypical absences and generalized myoclonic and/or bilateral tonic-clonic seizures. In contrast, the one individual carrying a loss-of-function variant had normal intelligence, no seizure history but has a diagnosis of autism spectrum disorder and suffering from elevated internalizing psychiatric symptoms.
Sources: Literature
Genetic Epilepsy v0.1316 GABRD Zornitza Stark Marked gene: GABRD as ready
Genetic Epilepsy v0.1316 GABRD Zornitza Stark Gene: gabrd has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1316 GABRD Zornitza Stark Classified gene: GABRD as Green List (high evidence)
Genetic Epilepsy v0.1316 GABRD Zornitza Stark Gene: gabrd has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1315 GABRD Zornitza Stark gene: GABRD was added
gene: GABRD was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: GABRD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABRD were set to 15115768; 34633442
Phenotypes for gene: GABRD were set to Intellectual disability; Epilepsy; Susceptibility to epilepsy, MIM#613060
Review for gene: GABRD was set to GREEN
Added comment: Susceptibility to epilepsy, MIM#613060: Limited reports. The variant originally reported in PMID 15115768 in association with epilepsy is present in >4,000 hets in gnomad and 55 homs which is not consistent with a Mendelian disorder.

PMID 34633442: 10 individuals with 7 unique variants reported in individuals with neurodevelopmental disorders and epilepsy. Six of the variants were demonstrated to be GoF, and those individuals with neurodevelopmental disorders with behavioural issues, various degrees of intellectual disability, generalized epilepsy with atypical absences and generalized myoclonic and/or bilateral tonic-clonic seizures. In contrast, the one individual carrying a loss-of-function variant had normal intelligence, no seizure history but has a diagnosis of autism spectrum disorder and suffering from elevated internalizing psychiatric symptoms.
Sources: Literature
Neurotransmitter Defects v1.5 GABRD Zornitza Stark Phenotypes for gene: GABRD were changed from Intellectual disability; Epilepsy; Susceptibility to epilepsy, MIM#613060 to Intellectual disability; Epilepsy; Susceptibility to epilepsy, MIM#613060
Neurotransmitter Defects v1.5 GABRD Zornitza Stark Phenotypes for gene: GABRD were changed from Intellectual disability; Epilepsy; Susceptibility to epilepsy, MIM#613060 to Intellectual disability; Epilepsy; Susceptibility to epilepsy, MIM#613060
Neurotransmitter Defects v1.4 GABRD Zornitza Stark Phenotypes for gene: GABRD were changed from Susceptibility to epilepsy, MIM#613060 to Intellectual disability; Epilepsy; Susceptibility to epilepsy, MIM#613060
Neurotransmitter Defects v1.3 GABRD Zornitza Stark Publications for gene: GABRD were set to 15115768
Neurotransmitter Defects v1.2 GABRD Zornitza Stark Classified gene: GABRD as Green List (high evidence)
Neurotransmitter Defects v1.2 GABRD Zornitza Stark Gene: gabrd has been classified as Green List (High Evidence).
Neurotransmitter Defects v1.1 GABRD Zornitza Stark changed review comment from: Limited reports. The variant originally reported in PMID 15115768 in association with epilepsy is present in >4,000 hets in gnomad and 55 homs which is not consistent with a Mendelian disorder.; to: Susceptibility to epilepsy, MIM#613060: Limited reports. The variant originally reported in PMID 15115768 in association with epilepsy is present in >4,000 hets in gnomad and 55 homs which is not consistent with a Mendelian disorder.
Neurotransmitter Defects v1.1 GABRD Zornitza Stark edited their review of gene: GABRD: Added comment: 10 individuals with 7 unique variants reported in individuals with neurodevelopmental disorders and epilepsy. Six of the variants were demonstrated to be GoF, and those individuals with neurodevelopmental disorders with behavioural issues, various degrees of intellectual disability, generalized epilepsy with atypical absences and generalized myoclonic and/or bilateral tonic-clonic seizures. In contrast, the one individual carrying a loss-of-function variant had normal intelligence, no seizure history but has a diagnosis of autism spectrum disorder and suffering from elevated internalizing psychiatric symptoms.; Changed rating: GREEN; Changed publications: 15115768, 34633442; Changed phenotypes: Intellectual disability, Epilepsy, Susceptibility to epilepsy, MIM#613060
Mendeliome v0.9373 GABRD Zornitza Stark Phenotypes for gene: GABRD were changed from Susceptibility to epilepsy, MIM#613060 to Susceptibility to epilepsy, MIM#613060
Mendeliome v0.9372 GABRD Zornitza Stark Publications for gene: GABRD were set to 15115768
Mendeliome v0.9371 GABRD Zornitza Stark Classified gene: GABRD as Green List (high evidence)
Mendeliome v0.9371 GABRD Zornitza Stark Gene: gabrd has been classified as Green List (High Evidence).
Mendeliome v0.9370 GABRD Zornitza Stark changed review comment from: Limited reports. The variant originally reported in PMID 15115768 in association with epilepsy is present in >4,000 hets in gnomad and 55 homs which is not consistent with a Mendelian disorder.; to: Susceptibility to epilepsy, MIM#613060: Limited reports. The variant originally reported in PMID 15115768 in association with epilepsy is present in >4,000 hets in gnomad and 55 homs which is not consistent with a Mendelian disorder.
Mendeliome v0.9370 GABRD Zornitza Stark edited their review of gene: GABRD: Added comment: 10 individuals with 7 unique variants reported in individuals with neurodevelopmental disorders and epilepsy. Six of the variants were demonstrated to be GoF, and those individuals with neurodevelopmental disorders with behavioural issues, various degrees of intellectual disability, generalized epilepsy with atypical absences and generalized myoclonic and/or bilateral tonic-clonic seizures. In contrast, the one individual carrying a loss-of-function variant had normal intelligence, no seizure history but has a diagnosis of autism spectrum disorder and suffering from elevated internalizing psychiatric symptoms.; Changed rating: GREEN; Changed publications: 15115768, 34633442; Changed phenotypes: Intellectual disability, Epilepsy, Susceptibility to epilepsy, MIM#613060
Imprinting disorders v0.10 NLRP7 Anna Le Fevre reviewed gene: NLRP7: Rating: GREEN; Mode of pathogenicity: None; Publications: 16462743, 28561018, 29574422, 19246479, 22315435, 19066229, 23722513; Phenotypes: Biparental complete hydatiform mole, Hydatiform mole, recurrent 1 MIM#231090, Multi locus imprinting disturbance in offspring, reproductive loss; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Arthrogryposis v0.300 ERGIC1 Arina Puzriakova reviewed gene: ERGIC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31230720; Phenotypes: Arthrogryposis multiplex congenita 2, neurogenic type, OMIM:208100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1314 CXorf56 Zornitza Stark Marked gene: CXorf56 as ready
Genetic Epilepsy v0.1314 CXorf56 Zornitza Stark Gene: cxorf56 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1314 CXorf56 Zornitza Stark Classified gene: CXorf56 as Green List (high evidence)
Genetic Epilepsy v0.1314 CXorf56 Zornitza Stark Gene: cxorf56 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1313 CXorf56 Zornitza Stark gene: CXorf56 was added
gene: CXorf56 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CXorf56 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: CXorf56 were set to 29374277; 31822863
Phenotypes for gene: CXorf56 were set to Mental retardation, X-linked 107, MIM# 301013
Review for gene: CXorf56 was set to GREEN
Added comment: Four families reported, seizures in males, who tend to be more severe.
Sources: Literature
Genetic Epilepsy v0.1312 CWF19L1 Zornitza Stark Marked gene: CWF19L1 as ready
Genetic Epilepsy v0.1312 CWF19L1 Zornitza Stark Gene: cwf19l1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1312 CWF19L1 Zornitza Stark gene: CWF19L1 was added
gene: CWF19L1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CWF19L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CWF19L1 were set to 33012273
Phenotypes for gene: CWF19L1 were set to Spinocerebellar ataxia, autosomal recessive 17, MIM# 616127
Review for gene: CWF19L1 was set to RED
Added comment: Well established gene-disease association, but only single report of epilepsy.
Sources: Literature
Mendeliome v0.9370 NLRP5 Zornitza Stark Phenotypes for gene: NLRP5 were changed from Early embryonic arrest to Early embryonic arrest; Multi locus imprinting disturbance in offspring
Mendeliome v0.9369 NLRP5 Zornitza Stark Publications for gene: NLRP5 were set to 32222962; 31829238; 30877238
Mendeliome v0.9368 NLRP5 Zornitza Stark Mode of inheritance for gene: NLRP5 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9367 NLRP5 Zornitza Stark Classified gene: NLRP5 as Green List (high evidence)
Mendeliome v0.9367 NLRP5 Zornitza Stark Gene: nlrp5 has been classified as Green List (High Evidence).
Mendeliome v0.9366 NLRP5 Zornitza Stark edited their review of gene: NLRP5: Added comment: 'Maternal effect gene'
Part of the subcortical maternal complex

Report of five mothers carrying either monoallelic or biallelic variants in NLRP5, who had both unaffected offspring and offspring with BWS-MLID (Doherty 2015). Report of one family where the mother carried biallelic variants in NLRP5, had one offspring with BWS, one unaffected offspring and multiple miscarriages (Sparago 2019).

Reports of at least three unrelated individuals with recurrent early embryonic arrest carrying biallelic variants in NLRP5. Functional work suggesting protein degradation in affected human cell lines (Mu 2019, Xu 2020).; Changed rating: GREEN; Changed publications: 32222962, 31829238, 30877238, 26323243, 34440388; Changed phenotypes: Early embryonic arrest, Multi locus imprinting disturbance in offspring; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Imprinting disorders v0.10 NLRP5 Zornitza Stark Marked gene: NLRP5 as ready
Imprinting disorders v0.10 NLRP5 Zornitza Stark Gene: nlrp5 has been classified as Green List (High Evidence).
Imprinting disorders v0.10 NLRP5 Zornitza Stark Publications for gene: NLRP5 were set to 26323243; 31201414; 31829238
Imprinting disorders v0.9 NLRP5 Zornitza Stark Mode of inheritance for gene: NLRP5 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4201 TNPO2 Zornitza Stark Phenotypes for gene: TNPO2 were changed from Intellectual disability, neurologic deficits and dysmorphic features to Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies, MIM# 619556
Intellectual disability syndromic and non-syndromic v0.4200 TNPO2 Zornitza Stark reviewed gene: TNPO2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies, MIM# 619556; Mode of inheritance: None
Genetic Epilepsy v0.1311 TNPO2 Zornitza Stark Phenotypes for gene: TNPO2 were changed from Intellectual disability, neurologic deficits and dysmorphic features to Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies, MIM# 619556
Genetic Epilepsy v0.1310 TNPO2 Zornitza Stark edited their review of gene: TNPO2: Changed phenotypes: Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies, MIM# 619556
Microcephaly v1.61 TNPO2 Zornitza Stark Phenotypes for gene: TNPO2 were changed from Intellectual disability, neurologic deficits and dysmorphic features to Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies, MIM# 619556
Microcephaly v1.60 TNPO2 Zornitza Stark edited their review of gene: TNPO2: Changed phenotypes: Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies, MIM# 619556
Mendeliome v0.9366 TNPO2 Zornitza Stark Phenotypes for gene: TNPO2 were changed from Intellectual disability, neurologic deficits and dysmorphic features to Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies, MIM# 619556
Mendeliome v0.9365 TNPO2 Zornitza Stark reviewed gene: TNPO2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies, MIM# 619556; Mode of inheritance: None
Imprinting disorders v0.8 NLRP5 Anna Le Fevre edited their review of gene: NLRP5: Added comment: Most reported individuals with recurrent early embryonic arrest or mothers of children with MLID have been found to carry biallelic pathogenic variants in this gene. A minority have only been found to carry a heterozygous variant only. A relationship between zygosity and severity of the condition has not been definitively established.

As is the case for other genes encoding components of the subcortical maternal complex (SCMC), the pathogenicity of variants can be difficult to establish as reproductive outcomes are not recorded in genomic databases and variants may be listed in population databases as they are not classed as pathogenic in males or women with no reproductive history.

Functional studies of genes encoding components of the SCMC are limited as their expression is restricted to the oocyte and early embryo.; Changed phenotypes: Early embryonic arrest, Multi locus imprinting disturbance in offspring
Growth failure v1.10 STAT5B Zornitza Stark Mode of inheritance for gene: STAT5B was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9365 DSTYK Zornitza Stark changed review comment from: Mono-allelic variants and CAKUT: Multiple families reported, zebrafish model has multiple congenital anomalies including of the GU tract. Established gene-disease association.

Bi-allelic variants and HSP: Three families reported, but all had same intragenic deletion/insertion, suggestive of founder effect.; to: Mono-allelic variants and CAKUT: Multiple families reported, zebrafish model has multiple congenital anomalies including of the GU tract. Disputed gene-disease association as original variants present at relatively high pop frequency as per review by Ain Roesley.

Bi-allelic variants and HSP: Three families reported, but all had same intragenic deletion/insertion, suggestive of founder effect.
Mendeliome v0.9365 DSTYK Zornitza Stark Mode of inheritance for gene: DSTYK was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9365 DSTYK Zornitza Stark Mode of inheritance for gene: DSTYK was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9364 DSTYK Ain Roesley reviewed gene: DSTYK: Rating: RED; Mode of pathogenicity: None; Publications: 23862974; Phenotypes: Congenital anomalies of kidney and urinary tract 1, MIM# 610805, Spastic paraplegia 23, MIM# 270750; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1310 CPT1A Zornitza Stark Marked gene: CPT1A as ready
Genetic Epilepsy v0.1310 CPT1A Zornitza Stark Gene: cpt1a has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1310 CPT1A Zornitza Stark Classified gene: CPT1A as Amber List (moderate evidence)
Genetic Epilepsy v0.1310 CPT1A Zornitza Stark Gene: cpt1a has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1309 CPT1A Zornitza Stark gene: CPT1A was added
gene: CPT1A was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: CPT1A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPT1A were set to 12189492; 33565078
Phenotypes for gene: CPT1A were set to CPT deficiency, hepatic, type IA, MIM# 255120
Review for gene: CPT1A was set to AMBER
Added comment: Well established gene-disease association.

CPT I deficiency is an autosomal recessive metabolic disorder of long-chain fatty acid oxidation characterized by severe episodes of hypoketotic hypoglycaemia usually occurring after fasting or illness. Onset is in infancy or early childhood.

Case report of presentation with seizures.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.4200 KCTD3 Zornitza Stark Marked gene: KCTD3 as ready
Intellectual disability syndromic and non-syndromic v0.4200 KCTD3 Zornitza Stark Gene: kctd3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4200 KCTD3 Zornitza Stark Phenotypes for gene: KCTD3 were changed from to Epilepsy; Intellectual disability; Posterior fossa abnormalities
Intellectual disability syndromic and non-syndromic v0.4199 KCTD3 Zornitza Stark Publications for gene: KCTD3 were set to
Intellectual disability syndromic and non-syndromic v0.4198 KCTD3 Zornitza Stark Mode of inheritance for gene: KCTD3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4197 KCTD3 Zornitza Stark reviewed gene: KCTD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 29406573; Phenotypes: Epilepsy, Intellectual disability, Posterior fossa abnormalities; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9364 KCTD3 Zornitza Stark Marked gene: KCTD3 as ready
Mendeliome v0.9364 KCTD3 Zornitza Stark Gene: kctd3 has been classified as Green List (High Evidence).
Mendeliome v0.9364 KCTD3 Zornitza Stark Phenotypes for gene: KCTD3 were changed from to Epilepsy; Intellectual disability; Posterior fossa abnormalities
Mendeliome v0.9363 KCTD3 Zornitza Stark Publications for gene: KCTD3 were set to
Genetic Epilepsy v0.1308 KCTD3 Zornitza Stark Marked gene: KCTD3 as ready
Genetic Epilepsy v0.1308 KCTD3 Zornitza Stark Gene: kctd3 has been classified as Green List (High Evidence).
Mendeliome v0.9362 KCTD3 Zornitza Stark Mode of inheritance for gene: KCTD3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1308 KCTD3 Zornitza Stark Phenotypes for gene: KCTD3 were changed from to Epilepsy; Intellectual disability; Posterior fossa abnormalities
Mendeliome v0.9361 KCTD3 Zornitza Stark reviewed gene: KCTD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 29406573; Phenotypes: Epilepsy, Intellectual disability, Posterior fossa abnormalities; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1307 KCTD3 Zornitza Stark Publications for gene: KCTD3 were set to
Genetic Epilepsy v0.1306 KCTD3 Zornitza Stark Mode of inheritance for gene: KCTD3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1305 KCTD3 Zornitza Stark reviewed gene: KCTD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 29406573; Phenotypes: Epilepsy, Intellectual disability, Posterior fossa abnormalities; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1305 POLR3B Zornitza Stark Marked gene: POLR3B as ready
Genetic Epilepsy v0.1305 POLR3B Zornitza Stark Gene: polr3b has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1305 POLR3B Zornitza Stark Classified gene: POLR3B as Green List (high evidence)
Genetic Epilepsy v0.1305 POLR3B Zornitza Stark Gene: polr3b has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1304 PPP1CB Zornitza Stark Marked gene: PPP1CB as ready
Genetic Epilepsy v0.1304 PPP1CB Zornitza Stark Gene: ppp1cb has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1304 PPP1CB Zornitza Stark Classified gene: PPP1CB as Amber List (moderate evidence)
Genetic Epilepsy v0.1304 PPP1CB Zornitza Stark Gene: ppp1cb has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9361 GYPC Zornitza Stark Marked gene: GYPC as ready
Mendeliome v0.9361 GYPC Zornitza Stark Gene: gypc has been classified as Red List (Low Evidence).
Mendeliome v0.9361 GYPC Zornitza Stark Phenotypes for gene: GYPC were changed from to [Blood group, Gerbich] MIM#616089
Mendeliome v0.9360 GYPC Zornitza Stark Publications for gene: GYPC were set to
Mendeliome v0.9359 GYPC Zornitza Stark Mode of inheritance for gene: GYPC was changed from Unknown to Other
Mendeliome v0.9358 GYPC Zornitza Stark Classified gene: GYPC as Red List (low evidence)
Mendeliome v0.9358 GYPC Zornitza Stark Gene: gypc has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1303 SMARCB1 Zornitza Stark Phenotypes for gene: SMARCB1 were changed from Coffin-Siris syndrome and epilepsy to Coffin-Siris syndrome 3, MIM# 614608; Epilepsy
Genetic Epilepsy v0.1302 SMARCB1 Zornitza Stark Classified gene: SMARCB1 as Green List (high evidence)
Genetic Epilepsy v0.1302 SMARCB1 Zornitza Stark Gene: smarcb1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1301 SMARCB1 Zornitza Stark Marked gene: SMARCB1 as ready
Genetic Epilepsy v0.1301 SMARCB1 Zornitza Stark Gene: smarcb1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1301 SMARCB1 Zornitza Stark Publications for gene: SMARCB1 were set to PMID:33006724
Genetic Epilepsy v0.1300 SMARCB1 Zornitza Stark Classified gene: SMARCB1 as Green List (high evidence)
Genetic Epilepsy v0.1300 SMARCB1 Zornitza Stark Gene: smarcb1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1299 SMARCB1 Zornitza Stark reviewed gene: SMARCB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22426308, 23906836, 23929686; Phenotypes: Coffin-Siris syndrome 3, MIM# 614608; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1299 SMARCB1 Zornitza Stark Classified gene: SMARCB1 as Red List (low evidence)
Genetic Epilepsy v0.1299 SMARCB1 Zornitza Stark Gene: smarcb1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.4197 TARS2 Zornitza Stark Marked gene: TARS2 as ready
Intellectual disability syndromic and non-syndromic v0.4197 TARS2 Zornitza Stark Gene: tars2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4197 TARS2 Zornitza Stark Phenotypes for gene: TARS2 were changed from Combined oxidative phosphorylation deficiency 21 - 615918; Epilepsy; Developmental Delay to Combined oxidative phosphorylation deficiency 21, MIM# 615918; Epilepsy; Developmental Delay
Intellectual disability syndromic and non-syndromic v0.4196 TARS2 Zornitza Stark Classified gene: TARS2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4196 TARS2 Zornitza Stark Gene: tars2 has been classified as Green List (High Evidence).
Mitochondrial disease v0.653 TARS2 Zornitza Stark Publications for gene: TARS2 were set to 24827421; 26811336; 33153448
Mitochondrial disease v0.652 TARS2 Zornitza Stark Classified gene: TARS2 as Green List (high evidence)
Mitochondrial disease v0.652 TARS2 Zornitza Stark Gene: tars2 has been classified as Green List (High Evidence).
Mendeliome v0.9357 TARS2 Zornitza Stark Publications for gene: TARS2 were set to 24827421; 26811336; 33153448
Mendeliome v0.9356 TARS2 Zornitza Stark Classified gene: TARS2 as Green List (high evidence)
Mendeliome v0.9356 TARS2 Zornitza Stark Gene: tars2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1298 SMARCA4 Zornitza Stark Marked gene: SMARCA4 as ready
Genetic Epilepsy v0.1298 SMARCA4 Zornitza Stark Gene: smarca4 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1298 SMARCA4 Zornitza Stark Classified gene: SMARCA4 as Red List (low evidence)
Genetic Epilepsy v0.1298 SMARCA4 Zornitza Stark Gene: smarca4 has been classified as Red List (Low Evidence).
Arthrogryposis v0.300 SLC29A3 Zornitza Stark Marked gene: SLC29A3 as ready
Arthrogryposis v0.300 SLC29A3 Zornitza Stark Gene: slc29a3 has been classified as Green List (High Evidence).
Arthrogryposis v0.300 SLC29A3 Zornitza Stark Classified gene: SLC29A3 as Green List (high evidence)
Arthrogryposis v0.300 SLC29A3 Zornitza Stark Gene: slc29a3 has been classified as Green List (High Evidence).
Arthrogryposis v0.299 SLC29A3 Zornitza Stark gene: SLC29A3 was added
gene: SLC29A3 was added to Arthrogryposis. Sources: Expert Review
Mode of inheritance for gene: SLC29A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC29A3 were set to 18940313; 19336477; 22238637
Phenotypes for gene: SLC29A3 were set to Histiocytosis-lymphadenopathy plus syndrome, MIM# 602782
Review for gene: SLC29A3 was set to GREEN
Added comment: Joint contractures are a feature.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.4195 ABHD16A Zornitza Stark reviewed gene: ABHD16A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.9355 GYPC Paul De Fazio reviewed gene: GYPC: Rating: RED; Mode of pathogenicity: None; Publications: 29469208; Phenotypes: [Blood group, Gerbich] MIM#616089; Mode of inheritance: Other; Current diagnostic: yes
Genetic Epilepsy v0.1297 SMARCB1 Belinda Chong gene: SMARCB1 was added
gene: SMARCB1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SMARCB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMARCB1 were set to PMID:33006724
Phenotypes for gene: SMARCB1 were set to Coffin-Siris syndrome and epilepsy
Review for gene: SMARCB1 was set to RED
Added comment: A single 8-year-old male with a p.Arg366Cys mutation of the SMARCB1 gene. Speech impairment and intellectual disability were reported. At the age of 6.3 years, he experienced his first generalized seizure during sleep. CBZ (16 mg/kg/day) was started and later switched to VPA (22 mg/kg/day) that could exert an additional role as a mood stabilizer, from which the hyperactive patient could benefit. Since then, he has been seizure-free. Brain MRI was normal.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4195 TARS2 Krithika Murali gene: TARS2 was added
gene: TARS2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: TARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TARS2 were set to 33153448; 24827421; 34508595
Phenotypes for gene: TARS2 were set to Combined oxidative phosphorylation deficiency 21 - 615918; Epilepsy; Developmental Delay
Review for gene: TARS2 was set to GREEN
Added comment: 8 cases from 7 unrelated families are reported in the literature with a heterogenous phenotype characterised by either early-onset illness within the first months, of severe hypotonia, failure to thrive, epilepsy and early death, or onset after six months with a milder course and longer survival. Other phenotypic features include developmental delay (at least 3 out of 8 cases), MRI-B abnormalities and more rarely dystonia, regression, hyperhidrosis and hearing impairment.
Sources: Literature
Mitochondrial disease v0.651 TARS2 Krithika Murali reviewed gene: TARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33153448, 24827421, 34508595; Phenotypes: Combined oxidative phosphorylation deficiency 21 - 615918, Epilepsy, Developmental Delay; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9355 TARS2 Krithika Murali reviewed gene: TARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33153448, 24827421, 34508595; Phenotypes: Combined oxidative phosphorylation deficiency 21 - 615918, Epilepsy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1297 SMARCA4 Belinda Chong gene: SMARCA4 was added
gene: SMARCA4 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SMARCA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMARCA4 were set to 33333793
Phenotypes for gene: SMARCA4 were set to Refractory seizures
Review for gene: SMARCA4 was set to RED
Added comment: A Wide Spectrum of Genetic Disorders Causing Severe Childhood Epilepsy in Taiwan: Single patient with seizure onset at 3months old (de novo variant c.3595G>A, p.Val199Met).
Sources: Literature
Short QT syndrome v1.3 KCNH2 Zornitza Stark Marked gene: KCNH2 as ready
Short QT syndrome v1.3 KCNH2 Zornitza Stark Gene: kcnh2 has been classified as Green List (High Evidence).
Short QT syndrome v1.3 KCNH2 Zornitza Stark Phenotypes for gene: KCNH2 were changed from to Short QT syndrome
Short QT syndrome v1.2 KCNH2 Zornitza Stark Publications for gene: KCNH2 were set to 34557911
Short QT syndrome v1.1 KCNQ1 Zornitza Stark Marked gene: KCNQ1 as ready
Short QT syndrome v1.1 KCNQ1 Zornitza Stark Gene: kcnq1 has been classified as Green List (High Evidence).
Short QT syndrome v1.1 KCNQ1 Zornitza Stark Phenotypes for gene: KCNQ1 were changed from to Short QT syndrome 1; bradycardia; atrial fibrillation
Genetic Epilepsy v0.1297 PPP1CB Ain Roesley gene: PPP1CB was added
gene: PPP1CB was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PPP1CB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PPP1CB were set to 33333793; 30236064
Phenotypes for gene: PPP1CB were set to Noonan syndrome-like disorder with loose anagen hair 2 MIM#617506
Penetrance for gene: PPP1CB were set to Complete
Review for gene: PPP1CB was set to AMBER
Added comment: PMID:33333793
1x de novo missense. Apnea, eye gazed deviation, myoclonic seizures

PMID:30236064
1x de novo missense. infant presented with severe intractable epileptic spasms

>20 individuals reported with this syndrome
Sources: Literature
Catecholaminergic Polymorphic Ventricular Tachycardia v0.30 TRDN Zornitza Stark Marked gene: TRDN as ready
Catecholaminergic Polymorphic Ventricular Tachycardia v0.30 TRDN Zornitza Stark Gene: trdn has been classified as Green List (High Evidence).
Catecholaminergic Polymorphic Ventricular Tachycardia v0.30 TRDN Zornitza Stark Phenotypes for gene: TRDN were changed from to Triadin knockout syndrome; CPVT; atypical LQTS phenotype
Catecholaminergic Polymorphic Ventricular Tachycardia v0.29 TRDN Zornitza Stark Publications for gene: TRDN were set to
Genetic Epilepsy v0.1297 POLR3B Ain Roesley gene: POLR3B was added
gene: POLR3B was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: POLR3B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: POLR3B were set to 33417887
Phenotypes for gene: POLR3B were set to ataxia, spasticity, and demyelinating neuropathy
Penetrance for gene: POLR3B were set to unknown
Review for gene: POLR3B was set to GREEN
Added comment: 3/6 individuals with de novo missense presented with seizures
Sources: Literature
Short QT syndrome v1.0 Zornitza Stark promoted panel to version 1.0
Short QT syndrome v0.13 KCNJ2 Zornitza Stark Marked gene: KCNJ2 as ready
Short QT syndrome v0.13 KCNJ2 Zornitza Stark Gene: kcnj2 has been classified as Green List (High Evidence).
Short QT syndrome v0.13 KCNJ2 Zornitza Stark Phenotypes for gene: KCNJ2 were changed from to Short QT syndrome
Genetic Epilepsy v0.1297 POU3F3 Ain Roesley gene: POU3F3 was added
gene: POU3F3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: POU3F3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: POU3F3 were set to 31303265; 33645921
Phenotypes for gene: POU3F3 were set to Snijders Blok-Fisher syndrome MIM#618604
Penetrance for gene: POU3F3 were set to unknown
Review for gene: POU3F3 was set to AMBER
Added comment: Seizures a rare feature. Only 3 out of 20 individuals presented with seizures.
Sources: Literature
Incidentalome v0.81 CACNA2D1 Zornitza Stark Marked gene: CACNA2D1 as ready
Incidentalome v0.81 CACNA2D1 Zornitza Stark Gene: cacna2d1 has been classified as Red List (Low Evidence).
Incidentalome v0.81 CACNA2D1 Zornitza Stark Tag disputed tag was added to gene: CACNA2D1.
Incidentalome v0.81 CACNA2D1 Zornitza Stark Mode of inheritance for gene: CACNA2D1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4195 THG1L Zornitza Stark Marked gene: THG1L as ready
Intellectual disability syndromic and non-syndromic v0.4195 THG1L Zornitza Stark Gene: thg1l has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1297 U2AF2 Zornitza Stark Marked gene: U2AF2 as ready
Genetic Epilepsy v0.1297 U2AF2 Zornitza Stark Added comment: Comment when marking as ready: Note de novo variants in this gene were found to be enriched in the DDD study, however phenotypic information on the patients not presented.
Genetic Epilepsy v0.1297 U2AF2 Zornitza Stark Gene: u2af2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1297 U2AF2 Zornitza Stark Marked gene: U2AF2 as ready
Genetic Epilepsy v0.1297 U2AF2 Zornitza Stark Gene: u2af2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1297 U2AF2 Zornitza Stark Classified gene: U2AF2 as Red List (low evidence)
Genetic Epilepsy v0.1297 U2AF2 Zornitza Stark Gene: u2af2 has been classified as Red List (Low Evidence).
Mendeliome v0.9355 SLC4A3 Daniel Flanagan gene: SLC4A3 was added
gene: SLC4A3 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: SLC4A3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC4A3 were set to PMID: 29167417; 34557911
Phenotypes for gene: SLC4A3 were set to Short QT syndrome
Review for gene: SLC4A3 was set to AMBER
Added comment: Moderate evidence for autosomal dominant short QT syndrome 1 by ClinGen /gene curation expert panel (PMID: 34557911). A single missense variant (absent gnomAD) identified in two SQTS families. In family 1, it segregated with SQTS (QTc<370ms) in 23 carriers, and 19 non-carriers had a QTc>370ms. In family 2, it segregated in 4 individuals. Experimental evidence from in vitro and zebrafish models suggests reduced membrane localization of the mutated protein leads to intracellular alkalinization and shortening of the cardiomyocyte action potential duration.
ClinGen expert panel was divided between strong (4 votes) and moderate (5 votes).
Sources: Expert Review
Incidentalome v0.80 CACNA2D1 Zornitza Stark Classified gene: CACNA2D1 as Red List (low evidence)
Incidentalome v0.80 CACNA2D1 Zornitza Stark Gene: cacna2d1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1296 RARS2 Zornitza Stark Marked gene: RARS2 as ready
Genetic Epilepsy v0.1296 RARS2 Zornitza Stark Gene: rars2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4195 THG1L Zornitza Stark Classified gene: THG1L as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.4195 THG1L Zornitza Stark Gene: thg1l has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1296 SLC22A5 Zornitza Stark Marked gene: SLC22A5 as ready
Genetic Epilepsy v0.1296 SLC22A5 Zornitza Stark Gene: slc22a5 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1296 RARS2 Zornitza Stark Phenotypes for gene: RARS2 were changed from to Pontocerebellar hypoplasia, type 6 MIM#611523
Catecholaminergic Polymorphic Ventricular Tachycardia v0.28 CASQ2 Zornitza Stark Mode of inheritance for gene: CASQ2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.1295 RARS2 Zornitza Stark Publications for gene: RARS2 were set to
Catecholaminergic Polymorphic Ventricular Tachycardia v0.27 TRDN Zornitza Stark Mode of inheritance for gene: TRDN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1294 RARS2 Zornitza Stark Mode of inheritance for gene: RARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Incidentalome v0.79 CACNA2D1 Daniel Flanagan reviewed gene: CACNA2D1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Short QT syndrome v0.12 CACNA1C Zornitza Stark Marked gene: CACNA1C as ready
Short QT syndrome v0.12 CACNA1C Zornitza Stark Gene: cacna1c has been classified as Red List (Low Evidence).
Short QT syndrome v0.12 SCN5A Zornitza Stark Marked gene: SCN5A as ready
Short QT syndrome v0.12 SCN5A Zornitza Stark Gene: scn5a has been classified as Red List (Low Evidence).
Short QT syndrome v0.12 KCNJ2 Zornitza Stark Publications for gene: KCNJ2 were set to
Short QT syndrome v0.12 CACNA1C Zornitza Stark Classified gene: CACNA1C as Red List (low evidence)
Short QT syndrome v0.12 CACNA1C Zornitza Stark Gene: cacna1c has been classified as Red List (Low Evidence).
Short QT syndrome v0.11 CACNA1C Zornitza Stark Tag disputed tag was added to gene: CACNA1C.
Short QT syndrome v0.11 CACNA2D1 Zornitza Stark Marked gene: CACNA2D1 as ready
Short QT syndrome v0.11 CACNA2D1 Zornitza Stark Gene: cacna2d1 has been classified as Red List (Low Evidence).
Short QT syndrome v0.11 CACNA2D1 Zornitza Stark Tag disputed tag was added to gene: CACNA2D1.
Short QT syndrome v0.11 SCN5A Zornitza Stark Classified gene: SCN5A as Red List (low evidence)
Short QT syndrome v0.11 SCN5A Zornitza Stark Gene: scn5a has been classified as Red List (Low Evidence).
Short QT syndrome v0.10 SCN5A Zornitza Stark Tag disputed tag was added to gene: SCN5A.
Short QT syndrome v0.10 CACNA2D1 Zornitza Stark Classified gene: CACNA2D1 as Red List (low evidence)
Short QT syndrome v0.10 CACNA2D1 Zornitza Stark Gene: cacna2d1 has been classified as Red List (Low Evidence).
Short QT syndrome v0.9 CACNB2 Zornitza Stark Marked gene: CACNB2 as ready
Short QT syndrome v0.9 CACNB2 Zornitza Stark Gene: cacnb2 has been classified as Red List (Low Evidence).
Short QT syndrome v0.9 CACNB2 Zornitza Stark Classified gene: CACNB2 as Red List (low evidence)
Short QT syndrome v0.9 CACNB2 Zornitza Stark Gene: cacnb2 has been classified as Red List (Low Evidence).
Short QT syndrome v0.8 CACNB2 Zornitza Stark Tag disputed tag was added to gene: CACNB2.
Genetic Epilepsy v0.1293 SLC22A5 Zornitza Stark Classified gene: SLC22A5 as Red List (low evidence)
Genetic Epilepsy v0.1293 SLC22A5 Zornitza Stark Gene: slc22a5 has been classified as Red List (Low Evidence).
Short QT syndrome v0.8 SLC22A5 Zornitza Stark Marked gene: SLC22A5 as ready
Short QT syndrome v0.8 SLC22A5 Zornitza Stark Gene: slc22a5 has been classified as Red List (Low Evidence).
Short QT syndrome v0.8 SLC22A5 Zornitza Stark Classified gene: SLC22A5 as Red List (low evidence)
Short QT syndrome v0.8 SLC22A5 Zornitza Stark Gene: slc22a5 has been classified as Red List (Low Evidence).
Short QT syndrome v0.7 SLC22A5 Zornitza Stark Tag disputed tag was added to gene: SLC22A5.
Genetic Epilepsy v0.1292 PNPT1 Zornitza Stark Marked gene: PNPT1 as ready
Genetic Epilepsy v0.1292 PNPT1 Zornitza Stark Gene: pnpt1 has been classified as Green List (High Evidence).
Short QT syndrome v0.7 SLC4A3 Zornitza Stark Marked gene: SLC4A3 as ready
Short QT syndrome v0.7 SLC4A3 Zornitza Stark Gene: slc4a3 has been classified as Amber List (Moderate Evidence).
Short QT syndrome v0.7 SLC4A3 Zornitza Stark Classified gene: SLC4A3 as Amber List (moderate evidence)
Short QT syndrome v0.7 SLC4A3 Zornitza Stark Gene: slc4a3 has been classified as Amber List (Moderate Evidence).
Short QT syndrome v0.6 SLC4A3 Zornitza Stark reviewed gene: SLC4A3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Short QT syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Short QT syndrome v0.6 KCNH2 Zornitza Stark Publications for gene: KCNH2 were set to 34557911
Short QT syndrome v0.6 KCNQ1 Zornitza Stark Publications for gene: KCNQ1 were set to 34557911
Genetic Epilepsy v0.1292 PNPT1 Zornitza Stark Phenotypes for gene: PNPT1 were changed from to Combined oxidative phosphorylation deficiency 13, MIM# 614932
Short QT syndrome v0.6 KCNJ2 Zornitza Stark Mode of pathogenicity for gene: KCNJ2 was changed from to Other
Short QT syndrome v0.5 KCNJ2 Zornitza Stark Mode of inheritance for gene: KCNJ2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4194 THG1L Krithika Murali gene: THG1L was added
gene: THG1L was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: THG1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: THG1L were set to 33682303
Phenotypes for gene: THG1L were set to Spinocerebellar ataxia, autosomal recessive 28 - 618800; Epilepsy; Intellectual Disability
Review for gene: THG1L was set to AMBER
Added comment: 3 individuals from 2 unrelated families of Ashkenazi Jewish descent with compound heterozygous variants ( p.Cys51Trp and p.Val55Ala) presented with profound developmental delays, microcephaly, intractable epilepsy, and cerebellar hypoplasia.

Homozygous variants associated with ataxia phenotype.
Sources: Literature
Short QT syndrome v0.4 KCNH2 Zornitza Stark Publications for gene: KCNH2 were set to
Short QT syndrome v0.4 KCNQ1 Zornitza Stark Publications for gene: KCNQ1 were set to
Genetic Epilepsy v0.1291 PNPT1 Zornitza Stark Classified gene: PNPT1 as Green List (high evidence)
Genetic Epilepsy v0.1291 PNPT1 Zornitza Stark Gene: pnpt1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1290 SLC22A5 Belinda Chong gene: SLC22A5 was added
gene: SLC22A5 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SLC22A5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC22A5 were set to PMID: 33005244
Phenotypes for gene: SLC22A5 were set to Intractable epilepsy
Review for gene: SLC22A5 was set to RED
Added comment: Two sisters with intractable epilepsy and reversible metabolic cardiomyopathy. Potential mutations in the SLC22A5 gene were investigated within the family, and a nonsense mutation [c.760C>T (p.R254X)] was identified in four family members. The two sisters harboured homozygous mutations, whereas their parents presented heterozygous mutations.

Metabolic disease screening revealed low plasma free carnitine levels (<5 µmol/l) in the two sisters. The plasma free carnitine levels of their parents were normal, and they were asymptomatic. PCD in the two patients was managed using oral levocarnitine.
Sources: Literature
Genetic Epilepsy v0.1290 PNPT1 Zornitza Stark reviewed gene: PNPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined oxidative phosphorylation deficiency 13, MIM# 614932; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Short QT syndrome v0.3 KCNH2 Zornitza Stark Mode of pathogenicity for gene: KCNH2 was changed from to Other
Short QT syndrome v0.3 KCNQ1 Zornitza Stark Mode of inheritance for gene: KCNQ1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Short QT syndrome v0.2 KCNH2 Zornitza Stark Mode of inheritance for gene: KCNH2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1290 PHF6 Zornitza Stark Marked gene: PHF6 as ready
Genetic Epilepsy v0.1290 PHF6 Zornitza Stark Gene: phf6 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1290 PHF6 Zornitza Stark Classified gene: PHF6 as Green List (high evidence)
Genetic Epilepsy v0.1290 PHF6 Zornitza Stark Gene: phf6 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1289 PGM3 Zornitza Stark Marked gene: PGM3 as ready
Genetic Epilepsy v0.1289 PGM3 Zornitza Stark Gene: pgm3 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1289 PGM3 Zornitza Stark Classified gene: PGM3 as Amber List (moderate evidence)
Genetic Epilepsy v0.1289 PGM3 Zornitza Stark Gene: pgm3 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1288 PGM3 Zornitza Stark reviewed gene: PGM3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Epilepsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1288 TARS2 Zornitza Stark Marked gene: TARS2 as ready
Genetic Epilepsy v0.1288 TARS2 Zornitza Stark Gene: tars2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1288 TARS2 Zornitza Stark Classified gene: TARS2 as Green List (high evidence)
Genetic Epilepsy v0.1288 TARS2 Zornitza Stark Gene: tars2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1287 TBX19 Zornitza Stark Marked gene: TBX19 as ready
Genetic Epilepsy v0.1287 TBX19 Zornitza Stark Gene: tbx19 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1287 TBX19 Zornitza Stark Classified gene: TBX19 as Green List (high evidence)
Genetic Epilepsy v0.1287 TBX19 Zornitza Stark Gene: tbx19 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1286 THG1L Zornitza Stark Marked gene: THG1L as ready
Genetic Epilepsy v0.1286 THG1L Zornitza Stark Gene: thg1l has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1286 TRAPPC12 Zornitza Stark Marked gene: TRAPPC12 as ready
Genetic Epilepsy v0.1286 TRAPPC12 Zornitza Stark Added comment: Comment when marking as ready: Three unrelated families with consistent phenotype including microcephaly and seizures.
Genetic Epilepsy v0.1286 TRAPPC12 Zornitza Stark Gene: trappc12 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1286 THG1L Zornitza Stark Phenotypes for gene: THG1L were changed from Spinocerebellar ataxia, autosomal recessive 28 - 618800; Epilepsy to Spinocerebellar ataxia, autosomal recessive 28 - 618800; Epilepsy; Intellectual disability
Genetic Epilepsy v0.1285 THG1L Zornitza Stark Classified gene: THG1L as Amber List (moderate evidence)
Genetic Epilepsy v0.1285 THG1L Zornitza Stark Gene: thg1l has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1284 TRAPPC12 Zornitza Stark Classified gene: TRAPPC12 as Green List (high evidence)
Genetic Epilepsy v0.1284 TRAPPC12 Zornitza Stark Gene: trappc12 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1283 TRPC3 Zornitza Stark Marked gene: TRPC3 as ready
Genetic Epilepsy v0.1283 TRPC3 Zornitza Stark Gene: trpc3 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1283 TRPC3 Zornitza Stark Classified gene: TRPC3 as Red List (low evidence)
Genetic Epilepsy v0.1283 TRPC3 Zornitza Stark Gene: trpc3 has been classified as Red List (Low Evidence).
Catecholaminergic Polymorphic Ventricular Tachycardia v0.26 CASQ2 Daniel Flanagan reviewed gene: CASQ2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: CPVT; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Catecholaminergic Polymorphic Ventricular Tachycardia v0.26 TRDN Daniel Flanagan reviewed gene: TRDN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Triadin knockout syndrome, CPVT, atypical LQTS phenotype; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic Epilepsy v0.1282 RARS2 Ain Roesley reviewed gene: RARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31536827; Phenotypes: Pontocerebellar hypoplasia, type 6 MIM#611523; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1282 COLGALT1 Zornitza Stark Marked gene: COLGALT1 as ready
Genetic Epilepsy v0.1282 COLGALT1 Zornitza Stark Gene: colgalt1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1282 COLGALT1 Zornitza Stark Classified gene: COLGALT1 as Amber List (moderate evidence)
Genetic Epilepsy v0.1282 COLGALT1 Zornitza Stark Gene: colgalt1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1281 COLGALT1 Zornitza Stark gene: COLGALT1 was added
gene: COLGALT1 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: COLGALT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COLGALT1 were set to 30412317; 33709034; 31759980
Phenotypes for gene: COLGALT1 were set to Brain small vessel disease 3 MIM#618360
Review for gene: COLGALT1 was set to AMBER
Added comment: 3 unrelated families with biallelic variants, and supporting functional assays. The main features of the cases were porencephalic cysts, leukoencephalopathy, lacunar infarcts, cerebral microbleeds/haemorrhages and calcifications. A null mouse model was embryonic lethal, but had defects in the vascular networks of the embryos.

Refractory seizures part of the presenting phenotype in one family.
Sources: Expert Review
Short QT syndrome v0.1 SCN5A Daniel Flanagan gene: SCN5A was added
gene: SCN5A was added to Short QT syndrome. Sources: Expert Review
Mode of inheritance for gene: SCN5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCN5A were set to PMID: 34557911
Phenotypes for gene: SCN5A were set to Short QT syndrome
Review for gene: SCN5A was set to RED
Added comment: Disputed association with Short QT syndrome 1 by ClinGen expert panel / PMID: 34557911. Single case with a rare SCN5A variant, however, the expert panel regarded this phenotype as being concordant with Brugada syndrome and not SQTS.
Sources: Expert Review
Short QT syndrome v0.1 CACNA1C Daniel Flanagan gene: CACNA1C was added
gene: CACNA1C was added to Short QT syndrome. Sources: Expert Review
Mode of inheritance for gene: CACNA1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CACNA1C were set to PMID: 34557911
Phenotypes for gene: CACNA1C were set to Short QT syndrome
Review for gene: CACNA1C was set to RED
Added comment: Disputed association with Short QT syndrome 1 by ClinGen expert panel / PMID: 34557911. 5 probands with suggested SQTS phenotype, 3 had Brugada syndrome with a relatively short QT interval, 1 had HCM without a convincing SQTS phenotype, and the 5th had a reported de novo variant that was too frequent in gnomAD to be associated with SQTS.
Sources: Expert Review
Short QT syndrome v0.1 CACNA2D1 Daniel Flanagan gene: CACNA2D1 was added
gene: CACNA2D1 was added to Short QT syndrome. Sources: Expert Review
Mode of inheritance for gene: CACNA2D1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CACNA2D1 were set to PMID: 34557911
Phenotypes for gene: CACNA2D1 were set to Short QT syndrome
Review for gene: CACNA2D1 was set to RED
Added comment: Disputed association with Short QT syndrome 1 by ClinGen expert panel / PMID: 34557911. Single case with cardiac arrest and a short QT interval, variant did not segregate with SQTS and it was present at >1% in the Ashkenazi Jewish population.
Sources: Expert Review
Short QT syndrome v0.1 CACNB2 Daniel Flanagan gene: CACNB2 was added
gene: CACNB2 was added to Short QT syndrome. Sources: Expert Review
Mode of inheritance for gene: CACNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CACNB2 were set to PMID: 34557911
Phenotypes for gene: CACNB2 were set to Short QT syndrome 1
Review for gene: CACNB2 was set to RED
Added comment: Disputed association with Short QT syndrome 1 by ClinGen expert panel / PMID: 34557911. Single case in which the expert panel concluded the phenotype was Brugada syndrome and not SQTS.
Sources: Expert Review
Short QT syndrome v0.1 SLC22A5 Daniel Flanagan gene: SLC22A5 was added
gene: SLC22A5 was added to Short QT syndrome. Sources: Expert Review
Mode of inheritance for gene: SLC22A5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC22A5 were set to PMID: 34557911
Phenotypes for gene: SLC22A5 were set to Short QT syndrome
Review for gene: SLC22A5 was set to RED
Added comment: SLC22A5 association with short QT syndrome is disputed by the ClinGen expert panel / PMID: 34557911. Variants in SLC22A5 cause AR primary systemic carnitine deficiency (PSCD). Short QC has been demonstrated in a carnitine-deficient mouse model as well as in patients with PSCD. However, the QT interval in these patients returns to normal with carnitine supplementation treatment, so true SQTS and SLC22A5 is disputed.
Sources: Expert Review
Genetic Epilepsy v0.1280 CLPB Zornitza Stark Marked gene: CLPB as ready
Genetic Epilepsy v0.1280 CLPB Zornitza Stark Gene: clpb has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1280 CLPB Zornitza Stark Classified gene: CLPB as Green List (high evidence)
Genetic Epilepsy v0.1280 CLPB Zornitza Stark Gene: clpb has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1279 CLPB Zornitza Stark gene: CLPB was added
gene: CLPB was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: CLPB was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CLPB were set to 25597510; 34140661
Phenotypes for gene: CLPB were set to 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropaenia, MIM# 616271
Review for gene: CLPB was set to GREEN
Added comment: Bi-allelic variants: 3-Methylglutaconic aciduria (MGCA7) is an autosomal recessive inborn error of metabolism characterized primarily by increased levels of 3-methylglutaconic acid (3-MGA) associated with neurologic deterioration and neutropenia. The phenotype is highly variable: most patients have infantile onset of a progressive encephalopathy with various movement abnormalities and delayed psychomotor development, although rare patients with normal neurologic development have been reported. Other common, but variable, features include cataracts, seizures, and recurrent infections. More than 10 unrelated families reported.

Mono-allelic variants: six unrelated individuals reported with de novo variants and neutropaenia, epilepsy, developmental issues, and 3-methylglutaconic aciduria.
Sources: Expert Review
Short QT syndrome v0.1 SLC4A3 Daniel Flanagan gene: SLC4A3 was added
gene: SLC4A3 was added to Short QT syndrome. Sources: Expert Review
Mode of inheritance for gene: SLC4A3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC4A3 were set to PMID: 29167417; 34557911
Phenotypes for gene: SLC4A3 were set to Short QT syndrome
Review for gene: SLC4A3 was set to GREEN
Added comment: Moderate evidence for autosomal dominant short QT syndrome 1 by ClinGen /gene curation expert panel (PMID: 34557911). A single missense variant (absent gnomAD) identified in two SQTS families. In family 1, it segregated with SQTS (QTc<370ms) in 23 carriers, and 19 non-carriers had a QTc>370ms. In family 2, it segregated in 4 individuals. Experimental evidence from in vitro and zebrafish models suggests reduced membrane localization of the mutated protein leads to intracellular alkalinization and shortening of the cardiomyocyte action potential duration.
ClinGen expert panel was divided between strong (4 votes) and moderate (5 votes).
Sources: Expert Review
Genetic Epilepsy v0.1278 CLN6 Zornitza Stark Marked gene: CLN6 as ready
Genetic Epilepsy v0.1278 CLN6 Zornitza Stark Gene: cln6 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1278 CLN6 Zornitza Stark Classified gene: CLN6 as Green List (high evidence)
Genetic Epilepsy v0.1278 CLN6 Zornitza Stark Gene: cln6 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1277 CLN6 Zornitza Stark gene: CLN6 was added
gene: CLN6 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: CLN6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLN6 were set to 11791207; 11727201; 21549341; 33798445; 33024953
Phenotypes for gene: CLN6 were set to Ceroid lipofuscinosis, neuronal, 6, MIM# 601780; Ceroid lipofuscinosis, neuronal, Kufs type, adult onset, MIM# 204300
Review for gene: CLN6 was set to GREEN
Added comment: Well established gene-disease association, seizures are part of the phenotype.
Sources: Expert Review
Short QT syndrome v0.1 KCNJ2 Daniel Flanagan reviewed gene: KCNJ2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 34557911; Phenotypes: Short QT syndrome 1; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Genetic Epilepsy v0.1276 PNPT1 Ain Roesley gene: PNPT1 was added
gene: PNPT1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PNPT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPT1 were set to 33158637; 31752325
Penetrance for gene: PNPT1 were set to unknown
Review for gene: PNPT1 was set to GREEN
Added comment: PMID:33158637
1x homozygous (c.1399C > T, p.Pro467Ser) in an individual who presented with a phenotype similar to Aicardi-Goutieres Syndrome. She presented with feeding difficulties and vomiting, muscle weakness, and hyperexcitability, accompanied by a sterile febrile episode. Later developed refractory focal impaired awareness and pharmaco-refractory generalized seizures.

PMID: 31752325
7 presented with seizures (out of 21 for whom clinical info was available)
Sources: Literature
Short QT syndrome v0.1 KCNQ1 Daniel Flanagan changed review comment from: Strong evidence for autosomal dominant short QT syndrome by ClinGen and gene curation expert panel (PMID: 34557911). 9 SQTS probands reported, eight of which had the p.(Val141Met) variant. All 9 probands presented with severe bradycardia in-utero or at birth and in 6 atrial fibrillation. Reviewed as strong because most of the evidence is related to a single variant.; to: Strong evidence for autosomal dominant short QT syndrome by ClinGen and gene curation expert panel (PMID: 34557911). 9 SQTS probands reported, eight of which had the p.(Val141Met) variant. All 9 probands presented with severe bradycardia in-utero or at birth and in 6 atrial fibrillation. Reviewed as strong because most of the evidence is related to a single variant.
Gain of function mechanism reported.
Short QT syndrome v0.1 KCNQ1 Daniel Flanagan reviewed gene: KCNQ1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34557911; Phenotypes: Short QT syndrome 1, bradycardia, atrial fibrillation; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Short QT syndrome v0.1 KCNH2 Daniel Flanagan reviewed gene: KCNH2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 34557911; Phenotypes: Short QT syndrome 1; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Genetic Epilepsy v0.1276 PHF6 Ain Roesley gene: PHF6 was added
gene: PHF6 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PHF6 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PHF6 were set to 32399860
Phenotypes for gene: PHF6 were set to Borjeson-Forssman-Lehmann syndrome MIM#301900
Penetrance for gene: PHF6 were set to unknown
Review for gene: PHF6 was set to GREEN
Added comment: Epilepsy is part of the phenotypic spectrum for Borjeson-Forssman-Lehmann syndrome (OMIM). At least 18 mutations known to date.
Sources: Literature
Genetic Epilepsy v0.1276 PGM3 Ain Roesley gene: PGM3 was added
gene: PGM3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PGM3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PGM3 were set to 33193641
Phenotypes for gene: PGM3 were set to Idiopathic focal epilepsy
Penetrance for gene: PGM3 were set to Incomplete
Review for gene: PGM3 was set to AMBER
Added comment: 4x unrelated families including 2x de novo +2x inherited from unaffected parents. Hence reduced penetrance suggested
3x missense, 1x protein truncating
both missense variants inherited from unaffected parents classified as VUS by ACMG guidelines

no functional studies done
Sources: Literature
Genetic Epilepsy v0.1276 TARS2 Krithika Murali gene: TARS2 was added
gene: TARS2 was added to Genetic Epilepsy. Sources: Expert list,Literature
Mode of inheritance for gene: TARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TARS2 were set to 33153448; 24827421; 34508595
Phenotypes for gene: TARS2 were set to Combined oxidative phosphorylation deficiency 21 - 615918; Epilepsy
Review for gene: TARS2 was set to GREEN
Added comment: 8 cases from 7 unrelated families are reported in the literature with early-onset mitochondrial encephalomyopathy and a broad phenotypic spectrum that includes epilepsy.
Sources: Expert list, Literature
Genetic Epilepsy v0.1276 TBX19 Krithika Murali gene: TBX19 was added
gene: TBX19 was added to Genetic Epilepsy. Sources: Expert list,Literature
Mode of inheritance for gene: TBX19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBX19 were set to 31998673
Phenotypes for gene: TBX19 were set to Adrenocorticotropic hormone deficiency - 201400
Review for gene: TBX19 was set to GREEN
Added comment: Well-established gene-disease association with congenital isolated ACTH deficiency. Affected individuals can present with seizures in conjunction with hypoglycaemia and cholestasis.

Although this gene is not associated with primary epilepsy and is a primary pituitary disorder, early detection and prompt institution of glucocorticoid treatment is vital to lower the risk of recurrent hypoglycemia and uncontrolled epilepsy. As patients can present with seizures, inclusion in this panel may aid timely diagnosis of this rare but treatable disorder.
Sources: Expert list, Literature
Genetic Epilepsy v0.1276 THG1L Krithika Murali gene: THG1L was added
gene: THG1L was added to Genetic Epilepsy. Sources: Expert list,Literature
Mode of inheritance for gene: THG1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: THG1L were set to 33682303
Phenotypes for gene: THG1L were set to Spinocerebellar ataxia, autosomal recessive 28 - 618800; Epilepsy
Review for gene: THG1L was set to AMBER
Added comment: 3 individuals from 2 unrelated families of Ashkenazi Jewish descent with compound heterozygous variants ( p.Cys51Trp and p.Val55Ala) presented with profound developmental delays, microcephaly, intractable epilepsy, and cerebellar hypoplasia.
Sources: Expert list, Literature
Genetic Epilepsy v0.1276 TRAPPC12 Krithika Murali reviewed gene: TRAPPC12: Rating: AMBER; Mode of pathogenicity: None; Publications: 28777934, 32369837; Phenotypes: Encephalopathy, progressive, early-onset, with brain atrophy and spasticity - 617669; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1276 TRPC3 Krithika Murali gene: TRPC3 was added
gene: TRPC3 was added to Genetic Epilepsy. Sources: Expert list,Literature
Mode of inheritance for gene: TRPC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRPC3 were set to 32135163; 25477146
Phenotypes for gene: TRPC3 were set to ?Spinocerebellar ataxia 41 - 616410
Review for gene: TRPC3 was set to RED
Added comment: Postulated association with adult-onset cerebellar ataxia based on one case with potentially pathogenic variant (Fogel et al Mov Disorder 2015)

Liang et al 2020 Neurosci Letter observed elevated TRPC3 protein expression in focal cortical dysplasia tissue specimens compared with controls.

No formal gene-disease association with epilepsy has been reported.
Sources: Expert list, Literature
Genetic Epilepsy v0.1276 MAPK8IP3 Zornitza Stark Marked gene: MAPK8IP3 as ready
Genetic Epilepsy v0.1276 MAPK8IP3 Zornitza Stark Gene: mapk8ip3 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1276 MAPK8IP3 Zornitza Stark Classified gene: MAPK8IP3 as Amber List (moderate evidence)
Genetic Epilepsy v0.1276 MAPK8IP3 Zornitza Stark Gene: mapk8ip3 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1275 MAPK8IP3 Elena Savva gene: MAPK8IP3 was added
gene: MAPK8IP3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: MAPK8IP3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MAPK8IP3 were set to PMID: 30612693
Phenotypes for gene: MAPK8IP3 were set to Neurodevelopmental disorder with or without variable brain abnormalities MIM#618443
Review for gene: MAPK8IP3 was set to AMBER
Added comment: 5/13 patients had generalized seizures, but for 3/13 it was a single event, 1/13 it was recurrent. All individuals had missense variants.
Sources: Literature
Hypophosphataemia or rickets v0.31 KL Bryony Thompson Publications for gene: KL were set to 18308935
Hypophosphataemia or rickets v0.30 KL Bryony Thompson Classified gene: KL as Amber List (moderate evidence)
Hypophosphataemia or rickets v0.30 KL Bryony Thompson Gene: kl has been classified as Amber List (Moderate Evidence).
Hypophosphataemia or rickets v0.29 KL Bryony Thompson edited their review of gene: KL: Added comment: 1 case reported with tumoral calcinosis and a homozygous missense, and 1 adult case reported with chronic kidney disease and hyperphosphatemia and a heterozygous frameshift variant. Also, supporting null mouse model.; Changed rating: AMBER; Changed publications: 18308935, 17710231, 31013726, 9363890; Changed phenotypes: Hypophosphatemic rickets, hyperparathyroidism, Tumoral calcinosis, hyperphosphatemic, familial, 3 MIM#617994, Hyperphosphatemia; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hypophosphataemia or rickets v0.28 CTNS Bryony Thompson Marked gene: CTNS as ready
Hypophosphataemia or rickets v0.28 CTNS Bryony Thompson Gene: ctns has been classified as Green List (High Evidence).
Hypophosphataemia or rickets v0.28 CTNS Bryony Thompson Classified gene: CTNS as Green List (high evidence)
Hypophosphataemia or rickets v0.28 CTNS Bryony Thompson Gene: ctns has been classified as Green List (High Evidence).
Hypophosphataemia or rickets v0.27 CTNS Bryony Thompson gene: CTNS was added
gene: CTNS was added to Hypophosphataemic Rickets. Sources: Expert list
Mode of inheritance for gene: CTNS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTNS were set to 20301574; 9537412; 31068690
Phenotypes for gene: CTNS were set to Cystinosis, nephropathic MIM#219800
Review for gene: CTNS was set to GREEN
gene: CTNS was marked as current diagnostic
Added comment: Hypophosphatemic rickets is a prominent feature of cystinosis when untreated.
Sources: Expert list
Hypophosphataemia or rickets v0.26 SGK3 Bryony Thompson Marked gene: SGK3 as ready
Hypophosphataemia or rickets v0.26 SGK3 Bryony Thompson Gene: sgk3 has been classified as Red List (Low Evidence).
Hypophosphataemia or rickets v0.26 SGK3 Bryony Thompson reviewed gene: SGK3: Rating: RED; Mode of pathogenicity: None; Publications: 31821448; Phenotypes: Hypophosphatemic rickets; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1275 TSPYL1 Zornitza Stark Marked gene: TSPYL1 as ready
Genetic Epilepsy v0.1275 TSPYL1 Zornitza Stark Gene: tspyl1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1275 TSPYL1 Zornitza Stark Classified gene: TSPYL1 as Green List (high evidence)
Genetic Epilepsy v0.1275 TSPYL1 Zornitza Stark Gene: tspyl1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.95 USP48 Zornitza Stark Marked gene: USP48 as ready
Deafness_IsolatedAndComplex v1.95 USP48 Zornitza Stark Gene: usp48 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.95 USP48 Zornitza Stark Classified gene: USP48 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.95 USP48 Zornitza Stark Gene: usp48 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.94 USP48 Zornitza Stark gene: USP48 was added
gene: USP48 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: USP48 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: USP48 were set to 34059922
Phenotypes for gene: USP48 were set to Nonsyndromic genetic deafness, MONDO:0019497
Review for gene: USP48 was set to GREEN
Added comment: PMID: 34059922 - Bassani et al 2021 - 3 cases reported with variants in USP48 and non syndromic hearing loss. They first analysed 4-generation Italian family with 6 individuals with hearing loss. The only rare variant segregating with the disease was a missense variant in USP48 (NM_032234.7:c.1216G > A, NP_115612.4:p.(Gly406Arg)). The variant is present in GnomAD v2.1.1 with a minor allele frequency (MAF) of 6.7 × 10−5 (17 allele out of 251 304 with no homozygotes). They also observed one hearing individual in the family who was heterozygous for the variant, suggesting incomplete penetrance.
In a Dutch family the found by exome sequencing a missense variant in USP48 (NM_032236.7:c.2215_2216delinsTT, NP_115612.4:p.(Thr739Leu)). The probands mother and uncle were also affected by no sequence data was available for analysis.
In a French family a proband is reported with right profound sensorineural hearing impairment (at 12 months), but normal left hearing (at 6 years old). The patient is heterozygote for a de novo splice variant in USP48 (NM_032236.7:c.3058 + 2 T > C, NP_115612.4:p.?;) which is not found in GnomAD and is predicted to result in a frameshift resulting in either NMD or a truncated protein.
In functional experiments they showed that the two missense variants found in the Italian and Dutch families, and a shortened protein as predicted for the variant found in the French variant, showed an impaired ability to cleave tetra-ubiquitin into tri-, di- and mono-ubiquitin. Using immunohistology, they show that the human USP48 protein is present in fetal inner ear specimens.
In addition zebrafish lacking usp48 showed a significant decrease of auditory response in acoustic startle response assays at 600 and 800 Hz wavelengths.

Overall, borderline Green: one of the variants is present at a high frequency in the normal population. However, even if just two families are considered, supportive functional data including zebrafish model.
Sources: Literature
Mendeliome v0.9355 USP48 Zornitza Stark Marked gene: USP48 as ready
Mendeliome v0.9355 USP48 Zornitza Stark Added comment: Comment when marking as ready: Borderline Green: one of the variants is present at a high frequency in the normal population. However, even if just two families are considered, supportive functional data including zebrafish model.
Mendeliome v0.9355 USP48 Zornitza Stark Gene: usp48 has been classified as Green List (High Evidence).
Mendeliome v0.9355 USP48 Zornitza Stark Classified gene: USP48 as Green List (high evidence)
Mendeliome v0.9355 USP48 Zornitza Stark Gene: usp48 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.33 MARS Zornitza Stark Marked gene: MARS as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.33 MARS Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved name is MARS1.
Pulmonary Fibrosis_Interstitial Lung Disease v0.33 MARS Zornitza Stark Gene: mars has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.33 MARS Zornitza Stark Tag new gene name tag was added to gene: MARS.
Mendeliome v0.9354 MARS Zornitza Stark Marked gene: MARS as ready
Mendeliome v0.9354 MARS Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved gene name is MARS1.
Mendeliome v0.9354 MARS Zornitza Stark Gene: mars has been classified as Green List (High Evidence).
Mendeliome v0.9354 MARS Zornitza Stark Tag new gene name tag was added to gene: MARS.
Chromosome Breakage Disorders v1.8 MARS Zornitza Stark Marked gene: MARS as ready
Chromosome Breakage Disorders v1.8 MARS Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved name is MARS1.
Chromosome Breakage Disorders v1.8 MARS Zornitza Stark Gene: mars has been classified as Red List (Low Evidence).
Chromosome Breakage Disorders v1.8 MARS Zornitza Stark Tag new gene name tag was added to gene: MARS.
Chromosome Breakage Disorders v1.8 MARS Zornitza Stark Marked gene: MARS as ready
Chromosome Breakage Disorders v1.8 MARS Zornitza Stark Gene: mars has been classified as Red List (Low Evidence).
Chromosome Breakage Disorders v1.8 MARS Zornitza Stark gene: MARS was added
gene: MARS was added to Chromosome Breakage Disorders. Sources: Literature
Mode of inheritance for gene: MARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MARS were set to 33909043
Phenotypes for gene: MARS were set to Trichothiodystrophy, MONDO:0018053
Review for gene: MARS was set to RED
Added comment: Bi-allelic ariants in this gene are associated with interstitial and liver disease.

PMID: 33909043 - Botta et al 2021 - using WES/WGS analysis of 34 unsolved cases with multi-system phenotypes, but with hair alterations that are typical of trichothiodystrophy but no reported photosensitivity, they identified a homozygous variant in one Italian patient (c.1201G > A (p.Val401Me) that is very rare (gnomAD frequency 0.00001414). Functional studies suggest that the variant affects gene product stability.

Although chromosome breakage is unlikely to be the underlying mechanism, included in this panel for completeness with a Red rating (one individual reported).
Sources: Literature
Mendeliome v0.9354 MARS Zornitza Stark Marked gene: MARS as ready
Mendeliome v0.9354 MARS Zornitza Stark Gene: mars has been classified as Green List (High Evidence).
Mendeliome v0.9354 MARS Zornitza Stark Phenotypes for gene: MARS were changed from to Interstitial lung and liver disease, MIM#615486; Charcot-Marie-Tooth disease, axonal, type 2U, MIM# 616280; Trichothiodystrophy, MONDO:0018053
Mendeliome v0.9353 MARS Zornitza Stark Publications for gene: MARS were set to
Mendeliome v0.9352 MARS Zornitza Stark Mode of inheritance for gene: MARS was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9351 MARS Zornitza Stark changed review comment from: Association with CMT: Two families reported. One mutation positive family member was asymptomatic. Second case is proband only testing with no segregation or functional data. Note one of the variants identified in dominant MARS1-associated neuropathy, p.Arg618Cys, has also been reported in AR MARS1-related pulmonary interstiatial/liver disease.; to: Association with CMT and mono-allelic variants: Two families reported. One mutation positive family member was asymptomatic. Second case is proband only testing with no segregation or functional data. Note one of the variants identified in dominant MARS1-associated neuropathy, p.Arg618Cys, has also been reported in AR MARS1-related pulmonary interstiatial/liver disease.
Mendeliome v0.9351 MARS Zornitza Stark changed review comment from: Association with interstitial lung and liver disease: More than 5 unrelated families reported. Founder variants in Reunion Island, p.Ser567Leu and p.Ala393Thr, in cis.

Pathologic examination of lung lavage is consistent with pulmonary alveolar proteinosis.; to: Association with interstitial lung and liver disease and bi-allelic variants: More than 5 unrelated families reported. Founder variants in Reunion Island, p.Ser567Leu and p.Ala393Thr, in cis.

Pathologic examination of lung lavage is consistent with pulmonary alveolar proteinosis.
Mendeliome v0.9351 MARS Zornitza Stark changed review comment from: Two families reported. One mutation positive family member was asymptomatic. Second case is proband only testing with no segregation or functional data. Note one of the variants identified in dominant MARS1-associated neuropathy, p.Arg618Cys, has also been reported in AR MARS1-related pulmonary interstiatial/liver disease.; to: Association with CMT: Two families reported. One mutation positive family member was asymptomatic. Second case is proband only testing with no segregation or functional data. Note one of the variants identified in dominant MARS1-associated neuropathy, p.Arg618Cys, has also been reported in AR MARS1-related pulmonary interstiatial/liver disease.
Mendeliome v0.9351 MARS Zornitza Stark edited their review of gene: MARS: Added comment: Association with interstitial lung and liver disease: More than 5 unrelated families reported. Founder variants in Reunion Island, p.Ser567Leu and p.Ala393Thr, in cis.

Pathologic examination of lung lavage is consistent with pulmonary alveolar proteinosis.; Changed rating: GREEN; Changed publications: 23729695, 24354524, 29655802, 24103465, 25913036; Changed phenotypes: Interstitial lung and liver disease, MIM#615486, Charcot-Marie-Tooth disease, axonal, type 2U, MIM# 616280; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.1274 TSPYL1 Krithika Murali gene: TSPYL1 was added
gene: TSPYL1 was added to Genetic Epilepsy. Sources: Expert list,Literature
Mode of inheritance for gene: TSPYL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TSPYL1 were set to 32885560; 15273283; 33075815
Phenotypes for gene: TSPYL1 were set to Sudden infant death with dysgenesis of the testes syndrome - 608800; sudden infant death-dysgenesis of the testes syndrome MONDO:0012124
Review for gene: TSPYL1 was set to GREEN
Added comment: First identified in a large Amish family - lethal disease characterized by sudden infant death from cardiorespiratory arrest with dysgenesis of the testes (Puffenberger et al 2004). Cases in non-Amish families reported with additional phenotypic features noted including epilepsy (Slater et al 2020 and Buyse et al 2020)
Sources: Expert list, Literature
Chromosome Breakage Disorders v1.7 AARS Zornitza Stark Marked gene: AARS as ready
Chromosome Breakage Disorders v1.7 AARS Zornitza Stark Gene: aars has been classified as Amber List (Moderate Evidence).
Chromosome Breakage Disorders v1.7 AARS Zornitza Stark Classified gene: AARS as Amber List (moderate evidence)
Chromosome Breakage Disorders v1.7 AARS Zornitza Stark Gene: aars has been classified as Amber List (Moderate Evidence).
Chromosome Breakage Disorders v1.6 AARS Zornitza Stark gene: AARS was added
gene: AARS was added to Chromosome Breakage Disorders. Sources: Literature
Mode of inheritance for gene: AARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AARS were set to 33909043
Phenotypes for gene: AARS were set to Trichothiodystrophy, MONDO:0018053
Review for gene: AARS was set to AMBER
Added comment: PMID: 33909043 - Botta et al 2021 - using WES or WGS analysis of 34 unsolved cases with multi-system phenotypes, but with hair alterations that are typical of trichothiodystrophy but no reported photosensitivity, they identified 2 unrelated cases carrying 4 potentially pathogenic variants in the AARS1 gene (previously known as AARSB). Both patients had very rare compound heterozygous missense variants. In one family there was an older affected sibling but segregation data was not available for either family. Functional studies suggest that the variants affects gene product stability.

Amber rating as 2 families only, and uncertain of underlying mechanism (unlikely chromosome breakage, gene is associated with other disease entities) but included due to phenotypic overlap.
Sources: Literature
Mendeliome v0.9351 AARS Zornitza Stark Phenotypes for gene: AARS were changed from Epileptic encephalopathy, early infantile, 29, MIM# 616339; Charcot-Marie-Tooth disease, axonal, type 2N, MIM# 613287 to Epileptic encephalopathy, early infantile, 29, MIM# 616339; Charcot-Marie-Tooth disease, axonal, type 2N, MIM# 613287; trichothiodystrophy, MONDO:0018053
Mendeliome v0.9350 AARS Zornitza Stark Publications for gene: AARS were set to 28493438; 25817015; 20045102; 22009580; 22206013; 30373780; 26032230
Intellectual disability syndromic and non-syndromic v0.4194 CELF2 Zornitza Stark Phenotypes for gene: CELF2 were changed from Developmental and epileptic encephalopathy to Developmental and epileptic encephalopathy 97, MIM#619561
Genetic Epilepsy v0.1274 CELF2 Zornitza Stark Phenotypes for gene: CELF2 were changed from Developmental and epileptic encephalopathy 97, MIM#619561 to Developmental and epileptic encephalopathy 97, MIM#619561
Intellectual disability syndromic and non-syndromic v0.4193 CELF2 Zornitza Stark edited their review of gene: CELF2: Changed phenotypes: Developmental and epileptic encephalopathy 97, MIM#619561
Genetic Epilepsy v0.1274 CELF2 Zornitza Stark Phenotypes for gene: CELF2 were changed from Developmental and epileptic encephalopathy to Developmental and epileptic encephalopathy 97, MIM#619561
Genetic Epilepsy v0.1273 CELF2 Zornitza Stark edited their review of gene: CELF2: Changed phenotypes: Developmental and epileptic encephalopathy 97, MIM#619561
Mendeliome v0.9349 CELF2 Zornitza Stark Phenotypes for gene: CELF2 were changed from Developmental and epileptic encephalopathy to Developmental and epileptic encephalopathy 97, MIM#619561
Mendeliome v0.9348 CELF2 Zornitza Stark edited their review of gene: CELF2: Changed phenotypes: Developmental and epileptic encephalopathy 97, MIM#619561
Defects of intrinsic and innate immunity v0.81 SPPL2A Zornitza Stark Phenotypes for gene: SPPL2A were changed from Susceptibility to mycobacteria and Salmonella to Immunodeficiency 86, MIM#619549; Susceptibility to mycobacteria and Salmonella
Defects of intrinsic and innate immunity v0.80 SPPL2A Zornitza Stark edited their review of gene: SPPL2A: Changed phenotypes: Immunodeficiency 86, MIM#619549, Susceptibility to mycobacteria and Salmonella
Mendeliome v0.9348 SPPL2A Zornitza Stark Phenotypes for gene: SPPL2A were changed from Susceptibility to mycobacteria and Salmonella to Immunodeficiency 86, MIM#619549; Susceptibility to mycobacteria and Salmonella
Mendeliome v0.9347 SPPL2A Zornitza Stark edited their review of gene: SPPL2A: Changed phenotypes: Immunodeficiency 86, MIM#619549, Susceptibility to mycobacteria and Salmonella
Mendeliome v0.9347 USP48 Eleanor Williams gene: USP48 was added
gene: USP48 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: USP48 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: USP48 were set to 34059922
Phenotypes for gene: USP48 were set to non-syndromic hearing loss; nonsyndromic genetic deafness, MONDO:0019497
Penetrance for gene: USP48 were set to Incomplete
Review for gene: USP48 was set to GREEN
Added comment: PMID: 34059922 - Bassani et al 2021 - 3 cases reported with variants in USP48 and non syndromic hearing loss. They first analysed 4-generation Italian family with 6 individuals with hearing loss. The only rare variant segregating with the disease was a missense variant in USP48 (NM_032234.7:c.1216G > A, NP_115612.4:p.(Gly406Arg)). The variant is present in GnomAD v2.1.1 with a minor allele frequency (MAF) of 6.7 × 10−5 (17 allele out of 251 304 with no homozygotes). They also observed one hearing individual in the family who was heterozygous for the variant, suggesting incomplete penetrance.
In a Dutch family the found by exome sequencing a missense variant in USP48 (NM_032236.7:c.2215_2216delinsTT, NP_115612.4:p.(Thr739Leu)). The probands mother and uncle were also affected by no sequence data was available for analysis.
In a French family a proband is reported with right profound sensorineural hearing impairment (at 12 months), but normal left hearing (at 6 years old). The patient is heterozygote for a de novo splice variant in USP48 (NM_032236.7:c.3058 + 2 T > C, NP_115612.4:p.?;) which is not found in GnomAD and is predicted to result in a frameshift resulting in either NMD or a truncated protein.
In functional experiments they showed that the two missense variants found in the Italian and Dutch families, and a shortened protein as predicted for the variant found in the French variant, showed an impaired ability to cleave tetra-ubiquitin into tri-, di- and mono-ubiquitin. Using immunohistology, they show that the human USP48 protein is present in fetal inner ear specimens.
In addition zebrafish lacking usp48 showed a significant decrease of auditory response in acoustic startle response assays at 600 and 800 Hz wavelengths.
Sources: Literature
Mendeliome v0.9347 MARS Eleanor Williams reviewed gene: MARS: Rating: ; Mode of pathogenicity: None; Publications: 33909043; Phenotypes: trichothiodystrophy, MONDO:0018053; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9347 AARS Eleanor Williams changed review comment from: PMID: 33909043 - Botta et al 2021 - using WES or WGS analysis of 34 unsolved cases with multi-system phenotypes, but with hair alterations that are typical of trichothiodystrophy but no reported photosensitivity, they identified 2 unrelated cases carrying 4 potentially pathogenic variants in the AARS1 gene (previously known as AARSB. Both patients had very rare compound heterozygous missense variants. In one family there was an older affected sibling but segregation data was not available for either family.; to: PMID: 33909043 - Botta et al 2021 - using WES or WGS analysis of 34 unsolved cases with multi-system phenotypes, but with hair alterations that are typical of trichothiodystrophy but no reported photosensitivity, they identified 2 unrelated cases carrying 4 potentially pathogenic variants in the AARS1 gene (previously known as AARSB. Both patients had very rare compound heterozygous missense variants. In one family there was an older affected sibling but segregation data was not available for either family. Functional studies suggest that the variants affects gene product stability.
Mendeliome v0.9347 AARS Eleanor Williams reviewed gene: AARS: Rating: ; Mode of pathogenicity: None; Publications: 33909043; Phenotypes: trichothiodystrophy, MONDO:0018053; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1273 CLN5 Zornitza Stark Marked gene: CLN5 as ready
Genetic Epilepsy v0.1273 CLN5 Zornitza Stark Gene: cln5 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1273 CLN5 Zornitza Stark Classified gene: CLN5 as Green List (high evidence)
Genetic Epilepsy v0.1273 CLN5 Zornitza Stark Gene: cln5 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1272 CLN5 Zornitza Stark gene: CLN5 was added
gene: CLN5 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: CLN5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLN5 were set to 32983231; 15728307; 20157158
Phenotypes for gene: CLN5 were set to Ceroid lipofuscinosis, neuronal, 5, MIM# 256731
Review for gene: CLN5 was set to GREEN
Added comment: Well established gene-disease association, initial presentation with seizures reported.
Sources: Expert Review
Cerebral Palsy v1.16 WDR45 Zornitza Stark Marked gene: WDR45 as ready
Cerebral Palsy v1.16 WDR45 Zornitza Stark Gene: wdr45 has been classified as Green List (High Evidence).
Cerebral Palsy v1.16 WDR45 Zornitza Stark Publications for gene: WDR45 were set to PMID: 33528536, 34364746
Additional findings_Paediatric v0.257 AIP Zornitza Stark reviewed gene: AIP: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.9347 AIP Zornitza Stark Marked gene: AIP as ready
Mendeliome v0.9347 AIP Zornitza Stark Gene: aip has been classified as Green List (High Evidence).
Mendeliome v0.9347 AIP Zornitza Stark Phenotypes for gene: AIP were changed from to Pituitary adenoma predisposition MIM#102200
Mendeliome v0.9346 AIP Zornitza Stark Publications for gene: AIP were set to
Mendeliome v0.9345 AIP Zornitza Stark Mode of inheritance for gene: AIP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9344 TTC26 Zornitza Stark Phenotypes for gene: TTC26 were changed from Ciliopathy Syndrome with Biliary, Renal, Neurological, and Skeletal Manifestations to Biliary, renal, neurologic, and skeletal syndrome, MIM# 619534; Ciliopathy Syndrome with Biliary, Renal, Neurological, and Skeletal Manifestations
Mendeliome v0.9343 TTC26 Zornitza Stark edited their review of gene: TTC26: Changed phenotypes: Biliary, renal, neurologic, and skeletal syndrome, MIM# 619534, Ciliopathy Syndrome with Biliary, Renal, Neurological, and Skeletal Manifestations
Ciliopathies v1.12 TTC26 Zornitza Stark Phenotypes for gene: TTC26 were changed from Ciliopathy Syndrome with Biliary, Renal, Neurological, and Skeletal Manifestations to Biliary, renal, neurologic, and skeletal syndrome, MIM# 619534; Ciliopathy Syndrome with Biliary, Renal, Neurological, and Skeletal Manifestations
Ciliopathies v1.11 TTC26 Zornitza Stark edited their review of gene: TTC26: Changed phenotypes: Biliary, renal, neurologic, and skeletal syndrome, MIM# 619534, Ciliopathy Syndrome with Biliary, Renal, Neurological, and Skeletal Manifestations
Cholestasis v0.205 TTC26 Zornitza Stark Phenotypes for gene: TTC26 were changed from Ciliopathy Syndrome with Biliary, Renal, Neurological, and Skeletal Manifestations to Biliary, renal, neurologic, and skeletal syndrome, MIM# 619534; Ciliopathy Syndrome with Biliary, Renal, Neurological, and Skeletal Manifestations
Cholestasis v0.204 TTC26 Zornitza Stark edited their review of gene: TTC26: Changed phenotypes: Biliary, renal, neurologic, and skeletal syndrome, MIM# 619534, Ciliopathy Syndrome with Biliary, Renal, Neurological, and Skeletal Manifestations
Intellectual disability syndromic and non-syndromic v0.4193 AP1G1 Zornitza Stark Phenotypes for gene: AP1G1 were changed from Neurodevelopmental disorder (NDD); Intellectual Disability; Epilepsy to Usmani-Riazuddin syndrome, autosomal dominant, MIM# 619467; Usmani-Riazuddin syndrome, autosomal recessive, MIM# 619548; Neurodevelopmental disorder (NDD); Intellectual Disability; Epilepsy
Intellectual disability syndromic and non-syndromic v0.4192 AP1G1 Zornitza Stark edited their review of gene: AP1G1: Changed phenotypes: Usmani-Riazuddin syndrome, autosomal dominant, MIM# 619467, Usmani-Riazuddin syndrome, autosomal recessive, MIM# 619548, Neurodevelopmental disorder (NDD), Intellectual Disability, Epilepsy
Genetic Epilepsy v0.1271 AP1G1 Zornitza Stark Phenotypes for gene: AP1G1 were changed from Neurodevelopmental disorder (NDD); Intellectual Disability; Epilepsy to Usmani-Riazuddin syndrome, autosomal dominant, MIM# 619467; Usmani-Riazuddin syndrome, autosomal recessive, MIM# 619548; Neurodevelopmental disorder (NDD); Intellectual Disability; Epilepsy
Genetic Epilepsy v0.1270 AP1G1 Zornitza Stark reviewed gene: AP1G1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Usmani-Riazuddin syndrome, autosomal dominant, MIM# 619467, Usmani-Riazuddin syndrome, autosomal recessive, MIM# 619548; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9343 AP1G1 Zornitza Stark Phenotypes for gene: AP1G1 were changed from Neurodevelopmental disorder (NDD); Intellectual Disability; Epilepsy to Usmani-Riazuddin syndrome, autosomal dominant, MIM# 619467; Usmani-Riazuddin syndrome, autosomal recessive, MIM# 619548; Neurodevelopmental disorder (NDD); Intellectual Disability; Epilepsy
Mendeliome v0.9342 AP1G1 Zornitza Stark edited their review of gene: AP1G1: Changed rating: GREEN; Changed phenotypes: Usmani-Riazuddin syndrome, autosomal dominant, MIM# 619467, Usmani-Riazuddin syndrome, autosomal recessive, MIM# 619548; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9342 CERKL Zornitza Stark Publications for gene: CERKL were set to 33322828; 32865075; 32411380
Retinitis pigmentosa v0.103 CERKL Zornitza Stark Marked gene: CERKL as ready
Retinitis pigmentosa v0.103 CERKL Zornitza Stark Gene: cerkl has been classified as Green List (High Evidence).
Retinitis pigmentosa v0.103 CERKL Zornitza Stark Phenotypes for gene: CERKL were changed from Retinitis pigmentosa 26, 608380 to Retinitis pigmentosa 26, MIM# 608380
Mendeliome v0.9341 CERKL Zornitza Stark edited their review of gene: CERKL: Changed publications: 33322828, 32865075, 32411380, 14681825, 24043777, 28838317, 27208204, 28130426
Retinitis pigmentosa v0.102 CERKL Zornitza Stark Publications for gene: CERKL were set to
Retinitis pigmentosa v0.101 CERKL Zornitza Stark reviewed gene: CERKL: Rating: GREEN; Mode of pathogenicity: None; Publications: 33322828, 32865075, 32411380; Phenotypes: Retinitis pigmentosa 26, MIM# 608380; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9341 CERKL Zornitza Stark Marked gene: CERKL as ready
Mendeliome v0.9341 CERKL Zornitza Stark Gene: cerkl has been classified as Green List (High Evidence).
Mendeliome v0.9341 CERKL Zornitza Stark Phenotypes for gene: CERKL were changed from Retinitis pigmentosa 26, MIM# 608380 to Retinitis pigmentosa 26, MIM# 608380
Mendeliome v0.9341 CERKL Zornitza Stark Phenotypes for gene: CERKL were changed from to Retinitis pigmentosa 26, MIM# 608380
Mendeliome v0.9340 CERKL Zornitza Stark Publications for gene: CERKL were set to
Mendeliome v0.9339 CERKL Zornitza Stark Mode of inheritance for gene: CERKL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9338 CERKL Zornitza Stark reviewed gene: CERKL: Rating: GREEN; Mode of pathogenicity: None; Publications: 33322828, 32865075, 32411380; Phenotypes: Retinitis pigmentosa 26, MIM# 608380; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9338 AIP Paul De Fazio changed review comment from: Germline variants in AIP cause predisposition to pituitary adenomas which may result in acromegaly.

A 2015 cohort study of 143 patients with pituitary gigantism who consented to genetic testing found 29% had variants in AIP. Age at first symptoms was 9-13 years, age at diagnosis 14-20 years.; to: Germline variants in AIP cause predisposition to pituitary adenomas which may result in acromegaly.

A 2015 cohort study of 143 patients with pituitary gigantism who consented to genetic testing found 29% had variants in AIP. Age at first symptoms was 9-13 years, age at diagnosis 14-20 years.

Many patients have no family history, suggesting low penetrance.
Additional findings_Paediatric v0.257 AIP Paul De Fazio reviewed gene: AIP: Rating: GREEN; Mode of pathogenicity: None; Publications: 16728643, 17360484, 26187128; Phenotypes: Pituitary adenoma predisposition MIM#102200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.9338 AIP Paul De Fazio reviewed gene: AIP: Rating: GREEN; Mode of pathogenicity: None; Publications: 16728643, 17360484, 26187128; Phenotypes: Pituitary adenoma predisposition MIM#102200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Cerebral vascular malformations v0.27 PIK3CA Zornitza Stark Marked gene: PIK3CA as ready
Cerebral vascular malformations v0.27 PIK3CA Zornitza Stark Gene: pik3ca has been classified as Green List (High Evidence).
Cerebral vascular malformations v0.27 PIK3CA Zornitza Stark Phenotypes for gene: PIK3CA were changed from Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome; Megalencephaly-capillary malformation-polymicrogyria syndrome, somatic; Megalencephaly-capillary malformation-polymicrogyria syndrome, somatic, 602501; Congenital Lipomatous Overgrowth, Vascular Malformations, and Epidermal Nevi; Cerebral Malformation Disorders to Cerebral cavernous malformations 4, MIM#619538
Cerebral vascular malformations v0.26 PIK3CA Zornitza Stark Publications for gene: PIK3CA were set to
Cerebral vascular malformations v0.25 PIK3CA Zornitza Stark Mode of inheritance for gene: PIK3CA was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.15 WDR45 Chirag Patel Classified gene: WDR45 as Green List (high evidence)
Cerebral Palsy v1.15 WDR45 Chirag Patel Gene: wdr45 has been classified as Green List (High Evidence).
Cerebral Palsy v1.15 WDR45 Chirag Patel Classified gene: WDR45 as Green List (high evidence)
Cerebral Palsy v1.15 WDR45 Chirag Patel Gene: wdr45 has been classified as Green List (High Evidence).
Cerebral vascular malformations v0.24 PIK3CA Zornitza Stark Classified gene: PIK3CA as Green List (high evidence)
Cerebral vascular malformations v0.24 PIK3CA Zornitza Stark Gene: pik3ca has been classified as Green List (High Evidence).
Cerebral Palsy v1.15 WDR45 Chirag Patel Classified gene: WDR45 as Green List (high evidence)
Cerebral Palsy v1.15 WDR45 Chirag Patel Gene: wdr45 has been classified as Green List (High Evidence).
Cerebral vascular malformations v0.23 PIK3CA Zornitza Stark Tag somatic tag was added to gene: PIK3CA.
Cerebral vascular malformations v0.23 PIK3CA Zornitza Stark reviewed gene: PIK3CA: Rating: GREEN; Mode of pathogenicity: None; Publications: 34496175; Phenotypes: Cerebral cavernous malformations 4, MIM#619538; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.14 WDR45 Chirag Patel gene: WDR45 was added
gene: WDR45 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: WDR45 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: WDR45 were set to PMID: 33528536, 34364746
Phenotypes for gene: WDR45 were set to Neurodegeneration with brain iron accumulation 5, OMIM # 300894
Review for gene: WDR45 was set to GREEN
Added comment: Established gene for neurodevelopmental/degenerative disorder with spasticity and dystonia. Moreno-De-Luca et al. (2021) reported 4 patients with CP with P/LP variants.
Zahrani et al. (2021) reported 2 patients with dystonic/hypotonic CP with variants.
Sources: Literature
Cerebral Palsy v1.13 ZEB2 Zornitza Stark Marked gene: ZEB2 as ready
Cerebral Palsy v1.13 ZEB2 Zornitza Stark Gene: zeb2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.13 ZEB2 Zornitza Stark Publications for gene: ZEB2 were set to PMID: 33528536, 33098801
Cerebral Palsy v1.12 UBE3A Zornitza Stark Marked gene: UBE3A as ready
Cerebral Palsy v1.12 UBE3A Zornitza Stark Gene: ube3a has been classified as Green List (High Evidence).
Cerebral Palsy v1.12 TUBB4A Zornitza Stark Marked gene: TUBB4A as ready
Cerebral Palsy v1.12 TUBB4A Zornitza Stark Gene: tubb4a has been classified as Green List (High Evidence).
Cerebral Palsy v1.12 TUBB4A Zornitza Stark Publications for gene: TUBB4A were set to PMID: 34531397, 33528536
Cerebral Palsy v1.11 TUBB2B Zornitza Stark Marked gene: TUBB2B as ready
Cerebral Palsy v1.11 TUBB2B Zornitza Stark Gene: tubb2b has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1270 CACNA1C Zornitza Stark Marked gene: CACNA1C as ready
Genetic Epilepsy v0.1270 CACNA1C Zornitza Stark Gene: cacna1c has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1270 CACNA1C Zornitza Stark Classified gene: CACNA1C as Green List (high evidence)
Genetic Epilepsy v0.1270 CACNA1C Zornitza Stark Gene: cacna1c has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1269 CACNA1C Zornitza Stark gene: CACNA1C was added
gene: CACNA1C was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CACNA1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CACNA1C were set to 34163037
Phenotypes for gene: CACNA1C were set to Neurodevelopmental abnormalities and epilepsy, no OMIM#
Review for gene: CACNA1C was set to GREEN
Added comment: Rodan et al. (2021) reported 25 individuals from 22 families with heterozygous truncating and missense variants in CACNA1C. The individuals presented with developmental delays, intellectual disability, autism, hypotonia, ataxia, and epilepsy BUT absence of classic features of Timothy syndrome or long QT syndrome. Functional studies of a subgroup of missense variants demonstrated loss of function, neutral effect, and gain of function on channel function in vitro.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4192 CACNA1C Zornitza Stark Publications for gene: CACNA1C were set to
Intellectual disability syndromic and non-syndromic v0.4191 CACNA1C Zornitza Stark Mode of inheritance for gene: CACNA1C was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9338 SHANK1 Zornitza Stark Marked gene: SHANK1 as ready
Mendeliome v0.9338 SHANK1 Zornitza Stark Gene: shank1 has been classified as Green List (High Evidence).
Mendeliome v0.9338 SHANK1 Zornitza Stark Phenotypes for gene: SHANK1 were changed from to Neurodevelopmental disorder, no OMIM#
Mendeliome v0.9337 SHANK1 Zornitza Stark Publications for gene: SHANK1 were set to
Cerebral Palsy v1.11 ZEB2 Chirag Patel Classified gene: ZEB2 as Green List (high evidence)
Cerebral Palsy v1.11 ZEB2 Chirag Patel Gene: zeb2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.11 ZEB2 Chirag Patel Classified gene: ZEB2 as Green List (high evidence)
Cerebral Palsy v1.11 ZEB2 Chirag Patel Gene: zeb2 has been classified as Green List (High Evidence).
Mendeliome v0.9336 SHANK1 Zornitza Stark Mode of inheritance for gene: SHANK1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9335 SHANK1 Zornitza Stark reviewed gene: SHANK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34113010, 22503632, 25188300; Phenotypes: Neurodevelopmental disorder, no OMIM#; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.11 ZEB2 Chirag Patel Classified gene: ZEB2 as Green List (high evidence)
Cerebral Palsy v1.11 ZEB2 Chirag Patel Gene: zeb2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.11 ZEB2 Chirag Patel Classified gene: ZEB2 as Green List (high evidence)
Cerebral Palsy v1.11 ZEB2 Chirag Patel Gene: zeb2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.10 ZEB2 Chirag Patel Classified gene: ZEB2 as Green List (high evidence)
Cerebral Palsy v1.10 ZEB2 Chirag Patel Gene: zeb2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.10 ZEB2 Chirag Patel Classified gene: ZEB2 as Green List (high evidence)
Cerebral Palsy v1.10 ZEB2 Chirag Patel Gene: zeb2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.10 ZEB2 Chirag Patel Classified gene: ZEB2 as Green List (high evidence)
Cerebral Palsy v1.10 ZEB2 Chirag Patel Gene: zeb2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4190 SHANK1 Zornitza Stark Phenotypes for gene: SHANK1 were changed from Autism to Neurodevelopmental disorder, no OMIM#
Intellectual disability syndromic and non-syndromic v0.4189 SHANK1 Zornitza Stark Publications for gene: SHANK1 were set to 22503632; 25188300
Intellectual disability syndromic and non-syndromic v0.4188 SHANK1 Zornitza Stark Mode of inheritance for gene: SHANK1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.9 ZEB2 Chirag Patel gene: ZEB2 was added
gene: ZEB2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ZEB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZEB2 were set to PMID: 33528536, 33098801
Phenotypes for gene: ZEB2 were set to Mowat-Wilson syndrome, OMIM # 235730
Review for gene: ZEB2 was set to GREEN
Added comment: Neurodevelopmental disorder with DD, ID, epilepsy, and dysmorphism.
Moreno-De-Luca et al. (2021) reported 3 patients with CP with P/LP variants.
Zech et al. (2020) reported 1 patient with dystonic CP with de novo variant.
Sources: Literature
Mendeliome v0.9335 GDF11 Zornitza Stark Classified gene: GDF11 as Green List (high evidence)
Mendeliome v0.9335 GDF11 Zornitza Stark Gene: gdf11 has been classified as Green List (High Evidence).
Mendeliome v0.9334 GDF11 Zornitza Stark edited their review of gene: GDF11: Added comment: Ravenscroft et al. (2021) report additional 6 probands who presented with craniofacial (5/6), vertebral (5/6), neurological (6/6), visual (4/6), cardiac (3/6), auditory (3/6), and connective tissue abnormalities (3/6). They found de novo and inherited variants in GDF11. gdf11 mutant zebrafish showed craniofacial abnormalities and body segmentation defects that matched some patient phenotypes. Expression of the patients’ variants in the fly showed that one nonsense variant in GDF11 is a severe loss-of-function (LOF) allele whereas the missense variants are partial LOF variants.; Changed rating: GREEN; Changed publications: 31215115, 34113007
Clefting disorders v0.144 GDF11 Zornitza Stark Publications for gene: GDF11 were set to PubMed: 31215115
Cerebral Palsy v1.8 UBE3A Chirag Patel Classified gene: UBE3A as Green List (high evidence)
Cerebral Palsy v1.8 UBE3A Chirag Patel Gene: ube3a has been classified as Green List (High Evidence).
Cerebral Palsy v1.7 UBE3A Chirag Patel gene: UBE3A was added
gene: UBE3A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: UBE3A was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene: UBE3A were set to PMID: 33528536
Phenotypes for gene: UBE3A were set to Angelman syndrome , OMIM #105830
Review for gene: UBE3A was set to GREEN
Added comment: Neurodevelopmental disorder with DD, ID, epilepsy, and ataxia. Moreno-De-Luca et al. (2021) reported 3 patients with CP with P/LP variants.
Sources: Literature
Genetic Epilepsy v0.1268 PLXNA1 Zornitza Stark Marked gene: PLXNA1 as ready
Genetic Epilepsy v0.1268 PLXNA1 Zornitza Stark Gene: plxna1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1268 PLXNA1 Zornitza Stark Classified gene: PLXNA1 as Green List (high evidence)
Genetic Epilepsy v0.1268 PLXNA1 Zornitza Stark Gene: plxna1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1267 PLXNA1 Zornitza Stark gene: PLXNA1 was added
gene: PLXNA1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PLXNA1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PLXNA1 were set to 34054129
Phenotypes for gene: PLXNA1 were set to Neurodevelopmental disorder with cerebral and eye anomalies
Review for gene: PLXNA1 was set to GREEN
Added comment: Dworschak et al. (2021) via WES reported 10 patients from 7 families with biallelic (n=7) or de novo (n=3) PLXNA1 variants. Shared phenotypic features include global developmental delay (9/10), brain anomalies (6/10), and eye anomalies (7/10). Seizures were predominantly reported in patients with monoallelic variants. Zebrafish studies showed an embryonic role of plxna1a in the development of the central nervous system and the eye. Biallelic variants in the extracellular Plexin-A1 domains lead to impaired dimerization or lack of receptor molecules, whereas monoallelic variants in the intracellular Plexin-A1 domains might impair downstream signaling through a dominant-negative effect.
Sources: Literature
Mendeliome v0.9334 PLXNA1 Zornitza Stark Marked gene: PLXNA1 as ready
Mendeliome v0.9334 PLXNA1 Zornitza Stark Gene: plxna1 has been classified as Green List (High Evidence).
Mendeliome v0.9334 PLXNA1 Zornitza Stark Classified gene: PLXNA1 as Green List (high evidence)
Mendeliome v0.9334 PLXNA1 Zornitza Stark Gene: plxna1 has been classified as Green List (High Evidence).
Mendeliome v0.9333 PLXNA1 Zornitza Stark gene: PLXNA1 was added
gene: PLXNA1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PLXNA1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PLXNA1 were set to 34054129
Phenotypes for gene: PLXNA1 were set to Neurodevelopmental disorder with cerebral and eye anomalies
Review for gene: PLXNA1 was set to GREEN
Added comment: Dworschak et al. (2021) via WES reported 10 patients from 7 families with biallelic (n=7) or de novo (n=3) PLXNA1 variants. Shared phenotypic features include global developmental delay (9/10), brain anomalies (6/10), and eye anomalies (7/10). Seizures were predominantly reported in patients with monoallelic variants. Zebrafish studies showed an embryonic role of plxna1a in the development of the central nervous system and the eye. Biallelic variants in the extracellular Plexin-A1 domains lead to impaired dimerization or lack of receptor molecules, whereas monoallelic variants in the intracellular Plexin-A1 domains might impair downstream signaling through a dominant-negative effect.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4187 PLXNA1 Zornitza Stark Marked gene: PLXNA1 as ready
Intellectual disability syndromic and non-syndromic v0.4187 PLXNA1 Zornitza Stark Gene: plxna1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.6 TUBB2B Chirag Patel reviewed gene: TUBB2B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.6 TUBB4A Chirag Patel Classified gene: TUBB4A as Green List (high evidence)
Cerebral Palsy v1.6 TUBB4A Chirag Patel Gene: tubb4a has been classified as Green List (High Evidence).
Cerebral Palsy v1.5 TUBB4A Chirag Patel Classified gene: TUBB4A as Green List (high evidence)
Cerebral Palsy v1.5 TUBB4A Chirag Patel Gene: tubb4a has been classified as Green List (High Evidence).
Cerebral Palsy v1.5 TUBB4A Chirag Patel Classified gene: TUBB4A as Green List (high evidence)
Cerebral Palsy v1.5 TUBB4A Chirag Patel Gene: tubb4a has been classified as Green List (High Evidence).
Cerebral Palsy v1.4 TUBB4A Chirag Patel gene: TUBB4A was added
gene: TUBB4A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TUBB4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB4A were set to PMID: 34531397, 33528536
Phenotypes for gene: TUBB4A were set to Dystonia 4, torsion, autosomal dominant, OMIM #128101; Leukodystrophy, hypomyelinating, 6, OMIM # 612438
Review for gene: TUBB4A was set to GREEN
Added comment: Van Eyk et al. (2021) reported 1 patient with dystonic CP with de novo variant. Moreno-De-Luca et al. (2021) reported 6 patients with CP with P/LP variants.
Sources: Literature
Cerebral Palsy v1.3 TUBB2B Chirag Patel Deleted their review
Cerebral Palsy v1.3 TUBB2B Chirag Patel gene: TUBB2B was added
gene: TUBB2B was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TUBB2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB2B were set to PMID: 33528536
Phenotypes for gene: TUBB2B were set to Cortical dysplasia, complex, with other brain malformations 7, OMIM # 610031
Review for gene: TUBB2B was set to RED
Added comment: Moreno-De-Luca et al. (2021) reported 3 patients with cerebral palsy with de novo pathogenic/LP variants BUT primarily presents with cortical malformations
Sources: Literature
Cerebral Palsy v1.2 TCF4 Chirag Patel Classified gene: TCF4 as Green List (high evidence)
Cerebral Palsy v1.2 TCF4 Chirag Patel Gene: tcf4 has been classified as Green List (High Evidence).
Cerebral Palsy v1.1 TCF4 Chirag Patel Classified gene: TCF4 as Green List (high evidence)
Cerebral Palsy v1.1 TCF4 Chirag Patel Gene: tcf4 has been classified as Green List (High Evidence).
Cerebral Palsy v1.1 TCF4 Chirag Patel Classified gene: TCF4 as Green List (high evidence)
Cerebral Palsy v1.1 TCF4 Chirag Patel Gene: tcf4 has been classified as Green List (High Evidence).
Cerebral Palsy v1.0 TCF4 Chirag Patel reviewed gene: TCF4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33528536; Phenotypes: Pitt-Hopkins syndrome, MIM# 610954; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4187 CACNA1C Chirag Patel reviewed gene: CACNA1C: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34163037; Phenotypes: Neurodevelopmental abnormalities and epilepsy, no OMIM#; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4187 SHANK1 Chirag Patel Classified gene: SHANK1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4187 SHANK1 Chirag Patel Gene: shank1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4186 SHANK1 Chirag Patel Classified gene: SHANK1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4186 SHANK1 Chirag Patel Gene: shank1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4185 SHANK1 Chirag Patel reviewed gene: SHANK1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34113010; Phenotypes: Neurodevelopmental disorder, no OMIM#; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting disorders v0.143 GDF11 Chirag Patel Classified gene: GDF11 as Green List (high evidence)
Clefting disorders v0.143 GDF11 Chirag Patel Gene: gdf11 has been classified as Green List (High Evidence).
Clefting disorders v0.142 GDF11 Chirag Patel edited their review of gene: GDF11: Added comment: Ravenscroft et al. (2021) report 6 probands who presented with craniofacial (5/6), vertebral (5/6), neurological (6/6), visual (4/6), cardiac (3/6), auditory (3/6), and connective tissue abnormalities (3/6). They found de novo and inherited variants in GDF11. gdf11 mutant zebrafish showed craniofacial abnormalities and body segmentation defects that matched some patient phenotypes. Expression of the patients’ variants in the fly showed that one nonsense variant in GDF11 is a severe loss-of-function (LOF) allele whereas the missense variants are partial LOF variants.; Changed rating: GREEN; Changed publications: PubMed: 31215115, 34113007; Changed phenotypes: Vertebral hypersegmentation and orofacial anomalies (VHO), OMIM #619122
Intellectual disability syndromic and non-syndromic v0.4185 PLXNA1 Chirag Patel Classified gene: PLXNA1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4185 PLXNA1 Chirag Patel Gene: plxna1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4184 PLXNA1 Chirag Patel gene: PLXNA1 was added
gene: PLXNA1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PLXNA1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PLXNA1 were set to PMID: 34054129
Phenotypes for gene: PLXNA1 were set to Neurodevelopmental disorder with cerebral and eye anomalies
Review for gene: PLXNA1 was set to GREEN
Added comment: Dworschak et al. (2021) via WES reported 10 patients from 7 families with biallelic (n=7) or de novo (n=3) PLXNA1 variants. Shared phenotypic features include global developmental delay (9/10), brain anomalies (6/10), and eye anomalies (7/10). Seizures were predominantly reported in patients with monoallelic variants. Zebrafish studies showed an embryonic role of plxna1a in the development of the central nervous system and the eye. Biallelic variants in the extracellular Plexin-A1 domains lead to impaired dimerization or lack of receptor molecules, whereas monoallelic variants in the intracellular Plexin-A1 domains might impair downstream signaling through a dominant-negative effect.
Sources: Literature
Cerebral Palsy v1.0 Zornitza Stark promoted panel to version 1.0
Cerebral Palsy v0.190 TCF4 Zornitza Stark Marked gene: TCF4 as ready
Cerebral Palsy v0.190 TCF4 Zornitza Stark Gene: tcf4 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v0.190 TCF4 Zornitza Stark Classified gene: TCF4 as Amber List (moderate evidence)
Cerebral Palsy v0.190 TCF4 Zornitza Stark Gene: tcf4 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v0.189 TCF4 Zornitza Stark gene: TCF4 was added
gene: TCF4 was added to Cerebral Palsy. Sources: Expert Review
Mode of inheritance for gene: TCF4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TCF4 were set to Pitt-Hopkins syndrome, MIM# 610954
Review for gene: TCF4 was set to AMBER
Added comment: Well established gene-disease association. Severe ID, seizures, dysmorphic features, but can be ataxic. Not specifically identified in CP cohorts.
Sources: Expert Review
Cerebral Palsy v0.188 STXBP1 Zornitza Stark Marked gene: STXBP1 as ready
Cerebral Palsy v0.188 STXBP1 Zornitza Stark Gene: stxbp1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.188 STXBP1 Zornitza Stark Classified gene: STXBP1 as Green List (high evidence)
Cerebral Palsy v0.188 STXBP1 Zornitza Stark Gene: stxbp1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.187 STXBP1 Zornitza Stark gene: STXBP1 was added
gene: STXBP1 was added to Cerebral Palsy. Sources: Expert Review
Mode of inheritance for gene: STXBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: STXBP1 were set to 29761117
Phenotypes for gene: STXBP1 were set to Developmental and epileptic encephalopathy 4, MIM# 612164
Review for gene: STXBP1 was set to GREEN
Added comment: ID and seizures, though spastic quadriplegia reported, and variants identified as part of CP cohorts.
Sources: Expert Review
Congenital nystagmus v0.4 CRX Zornitza Stark gene: CRX was added
gene: CRX was added to Congenital nystagmus. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: CRX was set to
Congenital nystagmus v0.4 GUCY2D Zornitza Stark gene: GUCY2D was added
gene: GUCY2D was added to Congenital nystagmus. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: GUCY2D was set to
Congenital nystagmus v0.4 AIPL1 Zornitza Stark gene: AIPL1 was added
gene: AIPL1 was added to Congenital nystagmus. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: AIPL1 was set to
Congenital nystagmus v0.4 SPATA7 Zornitza Stark gene: SPATA7 was added
gene: SPATA7 was added to Congenital nystagmus. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: SPATA7 was set to
Congenital nystagmus v0.4 RDH12 Zornitza Stark gene: RDH12 was added
gene: RDH12 was added to Congenital nystagmus. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: RDH12 was set to
Congenital nystagmus v0.4 RPGRIP1 Zornitza Stark gene: RPGRIP1 was added
gene: RPGRIP1 was added to Congenital nystagmus. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: RPGRIP1 was set to
Congenital nystagmus v0.4 CEP290 Zornitza Stark gene: CEP290 was added
gene: CEP290 was added to Congenital nystagmus. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: CEP290 was set to
Congenital nystagmus v0.4 ROM1 Zornitza Stark gene: ROM1 was added
gene: ROM1 was added to Congenital nystagmus. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: ROM1 was set to
Congenital nystagmus v0.4 GDF6 Zornitza Stark gene: GDF6 was added
gene: GDF6 was added to Congenital nystagmus. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: GDF6 was set to
Congenital nystagmus v0.4 IMPDH1 Zornitza Stark gene: IMPDH1 was added
gene: IMPDH1 was added to Congenital nystagmus. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: IMPDH1 was set to
Congenital nystagmus v0.4 USP45 Zornitza Stark gene: USP45 was added
gene: USP45 was added to Congenital nystagmus. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: USP45 was set to
Congenital nystagmus v0.4 PRPH2 Zornitza Stark gene: PRPH2 was added
gene: PRPH2 was added to Congenital nystagmus. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: PRPH2 was set to
Congenital nystagmus v0.4 TULP1 Zornitza Stark Source Expert Review Green was added to TULP1.
Source Expert list was added to TULP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Congenital nystagmus v0.4 LRAT Zornitza Stark gene: LRAT was added
gene: LRAT was added to Congenital nystagmus. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: LRAT was set to
Congenital nystagmus v0.4 KCNJ13 Zornitza Stark gene: KCNJ13 was added
gene: KCNJ13 was added to Congenital nystagmus. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: KCNJ13 was set to
Congenital nystagmus v0.4 RD3 Zornitza Stark gene: RD3 was added
gene: RD3 was added to Congenital nystagmus. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: RD3 was set to
Congenital nystagmus v0.4 CRB1 Zornitza Stark gene: CRB1 was added
gene: CRB1 was added to Congenital nystagmus. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: CRB1 was set to
Congenital nystagmus v0.4 RPE65 Zornitza Stark Source Expert list was added to RPE65.
Congenital nystagmus v0.4 NMNAT1 Zornitza Stark gene: NMNAT1 was added
gene: NMNAT1 was added to Congenital nystagmus. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: NMNAT1 was set to
Congenital nystagmus v0.4 RGS9BP Zornitza Stark gene: RGS9BP was added
gene: RGS9BP was added to Congenital nystagmus. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: RGS9BP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RGS9BP were set to 19818506; 14702087
Phenotypes for gene: RGS9BP were set to Bradyopsia MIM#608415
Congenital nystagmus v0.4 RGS9 Zornitza Stark gene: RGS9 was added
gene: RGS9 was added to Congenital nystagmus. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: RGS9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RGS9 were set to 10676965; 29107794; 14702087
Phenotypes for gene: RGS9 were set to Bradyopsia MIM#608415
Congenital nystagmus v0.4 PDE6H Zornitza Stark gene: PDE6H was added
gene: PDE6H was added to Congenital nystagmus. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: PDE6H was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDE6H were set to 22901948
Phenotypes for gene: PDE6H were set to Achromatopsia 6 MIM#610024
Congenital nystagmus v0.4 PDE6C Zornitza Stark gene: PDE6C was added
gene: PDE6C was added to Congenital nystagmus. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: PDE6C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDE6C were set to 19615668; 30080950
Phenotypes for gene: PDE6C were set to Cone dystrophy 4, MIM# 613093; Achromatopsia-5
Congenital nystagmus v0.4 GNAT2 Zornitza Stark gene: GNAT2 was added
gene: GNAT2 was added to Congenital nystagmus. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: GNAT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GNAT2 were set to 32203983; 17251445
Phenotypes for gene: GNAT2 were set to Achromatopsia 4 MIM#613856
Congenital nystagmus v0.4 CNGB3 Zornitza Stark gene: CNGB3 was added
gene: CNGB3 was added to Congenital nystagmus. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: CNGB3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNGB3 were set to 17265047
Phenotypes for gene: CNGB3 were set to Achromatopsia 3 MIM#262300
Congenital nystagmus v0.4 CNGA3 Zornitza Stark gene: CNGA3 was added
gene: CNGA3 was added to Congenital nystagmus. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: CNGA3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNGA3 were set to 9662398; 17265047; 11536077
Phenotypes for gene: CNGA3 were set to Achromatopsia 2 MIM#216900
Congenital nystagmus v0.4 ATF6 Zornitza Stark gene: ATF6 was added
gene: ATF6 was added to Congenital nystagmus. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: ATF6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATF6 were set to 26029869; 26063662
Phenotypes for gene: ATF6 were set to Achromatopsia 7 MIM#616517
Congenital nystagmus v0.4 ITM2B Zornitza Stark gene: ITM2B was added
gene: ITM2B was added to Congenital nystagmus. Sources: Expert list,Expert Review Red
Mode of inheritance for gene: ITM2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ITM2B were set to ?Retinal dystrophy with inner retinal dysfunction and ganglion cell abnormalities MIM#616079
Congenital nystagmus v0.4 TRPM1 Zornitza Stark gene: TRPM1 was added
gene: TRPM1 was added to Congenital nystagmus. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: TRPM1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRPM1 were set to Night blindness, congenital stationary (complete), 1C, autosomal recessive, 613216
Congenital nystagmus v0.4 SLC24A1 Zornitza Stark gene: SLC24A1 was added
gene: SLC24A1 was added to Congenital nystagmus. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: SLC24A1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC24A1 were set to Night blindness, congenital stationary (complete), 1D, autosomal recessive, 613830
Congenital nystagmus v0.4 SAG Zornitza Stark gene: SAG was added
gene: SAG was added to Congenital nystagmus. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: SAG was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SAG were set to Oguchi disease-1, MIM# 258100
Congenital nystagmus v0.4 RPE65 Zornitza Stark gene: RPE65 was added
gene: RPE65 was added to Congenital nystagmus. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: RPE65 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RPE65 were set to Leber Congenital Amaurosis; Leber congenital amaurosis 2, 204100; Leber congenital amaurosis 2; Retinitis pigmentosa 20
Congenital nystagmus v0.4 RIMS2 Zornitza Stark gene: RIMS2 was added
gene: RIMS2 was added to Congenital nystagmus. Sources: Expert Review Green,Literature
Mode of inheritance for gene: RIMS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RIMS2 were set to night blindness; Cone-rod synaptic disorder syndrome, congenital nonprogressive , MIM#618970; retinal dysfunction; nystagmus; autism
Congenital nystagmus v0.4 RHO Zornitza Stark gene: RHO was added
gene: RHO was added to Congenital nystagmus. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: RHO was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: RHO were set to Night blindness, congenital stationary autosomal dominant 1; Retinitis punctata albescens; Retinitis pigmentosa
Congenital nystagmus v0.4 RDH5 Zornitza Stark gene: RDH5 was added
gene: RDH5 was added to Congenital nystagmus. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: RDH5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RDH5 were set to Congenital Stationary Night Blindness; Fundus albipunctatus; Fundus albipunctatus, 136880; Achromatopsia, Cone, and Cone-rod Dystrophy
Congenital nystagmus v0.4 PDE6B Zornitza Stark gene: PDE6B was added
gene: PDE6B was added to Congenital nystagmus. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: PDE6B was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: PDE6B were set to Night blindness, congenital stationary, autosomal dominant 2, 163500; Retinitis pigmentosa
Congenital nystagmus v0.4 NYX Zornitza Stark gene: NYX was added
gene: NYX was added to Congenital nystagmus. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: NYX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: NYX were set to Night blindness, congenital stationary (complete), 1A, X-linked, 310500
Congenital nystagmus v0.4 LRIT3 Zornitza Stark gene: LRIT3 was added
gene: LRIT3 was added to Congenital nystagmus. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: LRIT3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LRIT3 were set to Night blindness, congenital stationary (complete), 1F, autosomal recessive, 615058
Congenital nystagmus v0.4 GRM6 Zornitza Stark gene: GRM6 was added
gene: GRM6 was added to Congenital nystagmus. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: GRM6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GRM6 were set to Night blindness, congenital stationary (complete), 1B, autosomal recessive, 257270
Congenital nystagmus v0.4 GRK1 Zornitza Stark gene: GRK1 was added
gene: GRK1 was added to Congenital nystagmus. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: GRK1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GRK1 were set to Oguchi disease-2, 613411
Congenital nystagmus v0.4 GPR179 Zornitza Stark gene: GPR179 was added
gene: GPR179 was added to Congenital nystagmus. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: GPR179 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GPR179 were set to Night blindness, congenital stationary (complete), 1E, autosomal recessive, 614565
Congenital nystagmus v0.4 GNB3 Zornitza Stark gene: GNB3 was added
gene: GNB3 was added to Congenital nystagmus. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: GNB3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GNB3 were set to Night blindness, congenital stationary, type 1H, MIM# 617024
Congenital nystagmus v0.4 GNAT1 Zornitza Stark gene: GNAT1 was added
gene: GNAT1 was added to Congenital nystagmus. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: GNAT1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: GNAT1 were set to Night blindness, congenital stationary, autosomal dominant 3, 610444
Congenital nystagmus v0.4 CHM Zornitza Stark gene: CHM was added
gene: CHM was added to Congenital nystagmus. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: CHM was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: CHM were set to Choroideremia (degeneration of the choriocapillaris, the retinal pigment epithelium, and the photoreceptor of the eye)
Congenital nystagmus v0.4 CACNA2D4 Zornitza Stark gene: CACNA2D4 was added
gene: CACNA2D4 was added to Congenital nystagmus. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: CACNA2D4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CACNA2D4 were set to Congenital Stationary Night Blindness; Retinal cone dystrophy 4, 610478
Congenital nystagmus v0.4 CACNA1F Zornitza Stark Source Royal Melbourne Hospital was added to CACNA1F.
Mode of inheritance for gene CACNA1F was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Added phenotypes Aland Island eye disease, 300600; Night blindness, congenital stationary (incomplete), 2A, X-linked, 300071; Cone-rod dystropy, X-linked, 3, 300476 for gene: CACNA1F
Congenital nystagmus v0.4 CABP4 Zornitza Stark gene: CABP4 was added
gene: CABP4 was added to Congenital nystagmus. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: CABP4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CABP4 were set to Night blindness, congenital stationary (incomplete), 2B, autosomal recessive, 610427
Congenital nystagmus v0.4 MITF Zornitza Stark Added phenotypes Waardenburg Syndrome Type 2 with Ocular Albinism (WS2-OA); Tietz Syndrome (TIETZS), Waardenburg Syndrome Type 2A (WS2A); Waardenburg syndrome/ocular albinism, digenic,103470 for gene: MITF
Congenital nystagmus v0.4 GNAI3 Zornitza Stark Added phenotypes Auriculocondylar syndrome 1 602483; Ocular Albinism for gene: GNAI3
Congenital nystagmus v0.4 DGUOK Zornitza Stark Added phenotypes Mitochondrial DNA depletion syndrome 3 for gene: DGUOK
Congenital nystagmus v0.4 TULP1 Zornitza Stark Added phenotypes Retinitis pigmentosa 14 600132 AR; Leber congenital amaurosis 15 613843 AR for gene: TULP1
Congenital nystagmus v0.4 MYO5A Zornitza Stark Added phenotypes Griscelli syndrome, type 1 214450 AR for gene: MYO5A
Congenital nystagmus v0.4 MLPH Zornitza Stark Added phenotypes Griscelli syndrome, type 3 609227 AR for gene: MLPH
Congenital nystagmus v0.4 MANBA Zornitza Stark Added phenotypes Mannosidosis, beta 248510 AR for gene: MANBA
Congenital nystagmus v0.4 LAMA1 Zornitza Stark Added phenotypes Poretti-Boltshauser syndrome, OMIM:615960 for gene: LAMA1
Congenital nystagmus v0.4 DTNBP1 Zornitza Stark Added phenotypes Hermansky-Pudlak syndrome 7 614076 AR for gene: DTNBP1
Congenital nystagmus v0.4 DCT Zornitza Stark Added phenotypes Ocutaneous albinism for gene: DCT
Congenital nystagmus v0.4 BLOC1S6 Zornitza Stark Added phenotypes ?Hermansky-pudlak syndrome 9 614171 AR for gene: BLOC1S6
Congenital nystagmus v0.4 BLOC1S5 Zornitza Stark Added phenotypes Hermansky-Pudlak syndrome, MONDO:0019312 for gene: BLOC1S5
Congenital nystagmus v0.4 BLOC1S3 Zornitza Stark Added phenotypes Hermansky-Pudlak syndrome 8, OMIM:614077, MONDO:0013560 for gene: BLOC1S3
Congenital nystagmus v0.4 AP3D1 Zornitza Stark Added phenotypes ?Hermansky-Pudlak syndrome 10 617050 AR for gene: AP3D1
Congenital nystagmus v0.4 AHR Zornitza Stark Added phenotypes Foveal hypoplasia without albinism; ?Retinitis pigmentosa 85, 618345; Infantile nystagmus for gene: AHR
Congenital nystagmus v0.4 TYRP1 Zornitza Stark Added phenotypes Oculocutaneous Albinism; Albinism, oculocutaneous, type III for gene: TYRP1
Congenital nystagmus v0.4 TYR Zornitza Stark Added phenotypes Albinism, oculocutaneous, type IA; Waardenburg syndrome/albinism, digenic; Oculocutaneous Albinism; Albinism, oculocutaneous, type IB for gene: TYR
Congenital nystagmus v0.4 SLC45A2 Zornitza Stark Added phenotypes Oculocutaneous Albinism; Oculocutaneous albinism type IV,606574; skin/hair/eye pigmentation 5,227240; Albinism, oculocutaneous, type IV for gene: SLC45A2
Congenital nystagmus v0.4 SLC38A8 Zornitza Stark Added phenotypes foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome MONDO:0012216; Foveal hypoplasia 2, with or without optic nerve misrouting and/or anterior segment dysgenesis OMIM:609218 for gene: SLC38A8
Congenital nystagmus v0.4 SLC24A5 Zornitza Stark Added phenotypes Non-Syndromic Oculocutaneous Albinism; Albinism, oculocutaneous, type VI for gene: SLC24A5
Congenital nystagmus v0.4 SETX Zornitza Stark Added phenotypes Amyotrophic lateral sclerosis 4, juvenile 602433 AD; Spinocerebellar ataxia, autosomal recessive 1 606002 AR for gene: SETX
Congenital nystagmus v0.4 SACS Zornitza Stark Added phenotypes Spastic ataxia, Charlevoix-Saguenay type 270550 AR for gene: SACS
Congenital nystagmus v0.4 RAB27A Zornitza Stark Added phenotypes Griscelli syndrome, type 2 607624 AR for gene: RAB27A
Congenital nystagmus v0.4 PAX6 Zornitza Stark Added phenotypes Aniridia 106210 AD; ?Coloboma of optic nerve 120430 AD; ?Morning glory disc anomaly 120430 AD; ?Coloboma, ocular 120200 AD; Anterior segment dysgenesis 5, multiple subtypes 604229; Keratitis 148190 AD; Optic nerve hypoplasia 165550 AD; Cataract with late-onset corneal dystrophy 106210 AD; Foveal hypoplasia 1 136520 AD for gene: PAX6
Congenital nystagmus v0.4 OCA2 Zornitza Stark Added phenotypes Skin/hair/eye pigmentation 1, blond/brown hair; Albinism, oculocutaneous, type II; Oculocutaneous Albinism; Skin/hair/eye pigmentation 1, blue/nonblue eyes; Albinism, brown oculocutaneous for gene: OCA2
Congenital nystagmus v0.4 LYST Zornitza Stark Added phenotypes optic neuropathy with progressive vision loss; Chediak-Higashi syndrome; oculo-cutaneous albinism for gene: LYST
Congenital nystagmus v0.4 LRMDA Zornitza Stark Added phenotypes Albinism, oculocutaneous, type VII for gene: LRMDA
Congenital nystagmus v0.4 HPS6 Zornitza Stark Added phenotypes Hermansky-Pudlak syndrome 6 614075 AR for gene: HPS6
Congenital nystagmus v0.4 HPS5 Zornitza Stark Added phenotypes Hermansky-Pudlak syndrome 5 for gene: HPS5
Congenital nystagmus v0.4 HPS4 Zornitza Stark Added phenotypes Hermansky-Pudlak syndrome 4 for gene: HPS4
Congenital nystagmus v0.4 HPS3 Zornitza Stark Added phenotypes Hermansky-Pudlak syndrome 3 for gene: HPS3
Congenital nystagmus v0.4 HPS1 Zornitza Stark Added phenotypes Hermansky-Pudlak syndrome 1 for gene: HPS1
Congenital nystagmus v0.4 GPR143 Zornitza Stark Added phenotypes Ocular albinism, type I; Nystagmus 6, congenital, X-linked, 300814; Ocular albinism, type I, Nettleship-Falls type, 300500 for gene: GPR143
Congenital nystagmus v0.4 FRMD7 Zornitza Stark Added phenotypes Nystagmus 1, Congenital, X-Linked; Nystagmus 1, congenital, X-linked, 310700; Infantile Nystagmus; (not relevant if inheritance through paternal line); Nystagmus, infantile periodic alternating, X-linked, 310700 for gene: FRMD7
Congenital nystagmus v0.4 CASK Zornitza Stark Added phenotypes Mental retardation, with or without nystagmus 300422; FG syndrome 4 300422; Mental retardation and microcephaly with pontine and cerebellar hypoplasia 300749 XLD for gene: CASK
Congenital nystagmus v0.4 CACNA1F Zornitza Stark Added phenotypes Cone-rod dystrophy, X-linked, 3 300476 XLR; Aland Island eye disease 300600 XL; Night blindness, congenital stationary (incomplete), 2A, X-linked 300071 XL for gene: CACNA1F
Congenital nystagmus v0.4 CACNA1A Zornitza Stark Added phenotypes Acetazolamide-Responsive Hereditary Paroxysmal Cerebellar Ataxia; CACNA1A-Related Episodic Ataxia Type 2; Episodic Ataxia Type 2 (EA2) Episodic Ataxia, Nystagmus-Associated for gene: CACNA1A
Congenital nystagmus v0.4 AP3B1 Zornitza Stark Added phenotypes Hermansky-Pudlak syndrome 2 608233 AR for gene: AP3B1
Congenital nystagmus v0.3 Zornitza Stark Panel name changed from Albinism or congenital nystagmus to Congenital nystagmus
Genetic Epilepsy v0.1266 TUBGCP6 Zornitza Stark Marked gene: TUBGCP6 as ready
Genetic Epilepsy v0.1266 TUBGCP6 Zornitza Stark Gene: tubgcp6 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1266 TUBGCP6 Zornitza Stark Classified gene: TUBGCP6 as Green List (high evidence)
Genetic Epilepsy v0.1266 TUBGCP6 Zornitza Stark Gene: tubgcp6 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1265 TUBGCP6 Krithika Murali gene: TUBGCP6 was added
gene: TUBGCP6 was added to Genetic Epilepsy. Sources: Expert list,Literature
Mode of inheritance for gene: TUBGCP6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TUBGCP6 were set to 22279524; 33453472
Phenotypes for gene: TUBGCP6 were set to Microcephaly and chorioretinopathy, autosomal recessive, 1 - 251270; Epilepsy
Review for gene: TUBGCP6 was set to GREEN
Added comment: Known association with congenital microcephaly, developmental delay and retinal disorders with epilepsy also reported in some individuals.
Sources: Expert list, Literature
Genetic Epilepsy v0.1265 CLCN2 Zornitza Stark Marked gene: CLCN2 as ready
Genetic Epilepsy v0.1265 CLCN2 Zornitza Stark Gene: clcn2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1265 CLCN2 Zornitza Stark Tag disputed tag was added to gene: CLCN2.
Genetic Epilepsy v0.1265 CLCN2 Zornitza Stark gene: CLCN2 was added
gene: CLCN2 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: CLCN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLCN2 were set to 23707145; 19191339; 20037607; 19710712
Phenotypes for gene: CLCN2 were set to {Epilepsy, juvenile myoclonic, susceptibility to, 8}, 607628; {Epilepsy, juvenile absence, susceptibility to, 2}, 607628; {Epilepsy, idiopathic generalized, susceptibility to, 11}, 607628
Review for gene: CLCN2 was set to RED
Added comment: Conflicting evidence regarding association with epilepsy syndromes, including one retracted paper.

In 3 of 46 unrelated families with IGE localized to 3q26, Haug et al. (2003) identified 3 mutations in the CLCN2 gene. In a re-evaluation of 2 of the families reported by Haug et al. (2003), Kleefuss-Lie et al. (2009) found discrepancies in the family structure, phenotype, and genetic analysis. On this basis, all but one of the original authors retracted the paper.

Stogmann et al. (2006) did not identify pathogenic mutations in the CLCN2 gene in 61 patients with IGE or 35 patients with temporal lobe epilepsy, suggesting that CLCN2 gene mutations are not a common cause of these disorders.

By sequencing of a large collection of human DNA followed by electrophysiologic analysis, Blanz et al. (2007) concluded that several CLCN2 sequence abnormalities previously found in patients with epilepsy most likely represented benign polymorphisms.

Saint-Martin et al. (2009) identified 2 different heterozygous variants in the CLCN2 gene in affected members of 2 unrelated families with juvenile myoclonic epilepsy (EJM8) and idiopathic generalized epilepsy (EIG11), respectively. In both families, the unaffected father also had the variant, suggesting either reduced penetrance or additional unidentified factors necessary for full phenotypic expression.

Niemeyer et al. (2010) disagreed with the conclusion by Kleefuss-Lie et al. (2009) that some of the work by Haug et al. (2003) had merit. Based on lack of functional consequences of the variants reported by Haug et al. (2003), Niemeyer et al. (2010) asserted that there is no evidence for a role of CLCN2 variants in idiopathic generalized epilepsy.
Sources: Expert Review
Genetic Epilepsy v0.1264 CHRM1 Zornitza Stark Marked gene: CHRM1 as ready
Genetic Epilepsy v0.1264 CHRM1 Zornitza Stark Gene: chrm1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1264 CHRM1 Zornitza Stark gene: CHRM1 was added
gene: CHRM1 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: CHRM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHRM1 were set to 34212451; 31981491; 12483218
Phenotypes for gene: CHRM1 were set to Neurodevelopmental disorder; intellectual disability; autism; epilepsy
Review for gene: CHRM1 was set to RED
Added comment: PMID: 34212451 - 2 unrelated cases with de novo missense variants (p.Pro380Leu and p.Phe425Ser), one case with early-onset refractory epilepsy, severe disability, and progressive cerebral and cerebellar atrophy, and the second case with mild dysmorphism, global developmental delay, and moderate intellectual disability. In vitro biochemical analyses of p.Pro380Leu demonstrated a reduction in protein levels, impaired cellular trafficking, and defective activation of intracellular signaling pathways.
PMID: 31981491 - an autism spectrum disorder (no other information on phenotype, except ascertained to have severe neurodevelopmental delay) case with a de novo missense variant p.(Arg210Leu)
PMID: 12483218 - null mouse model assessing memory demonstrated selective cognitive dysfunction.
Sources: Expert Review
Genetic Epilepsy v0.1263 U2AF2 Krithika Murali gene: U2AF2 was added
gene: U2AF2 was added to Genetic Epilepsy. Sources: Expert list,Literature
Mode of inheritance for gene: U2AF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: U2AF2 were set to 34112922
Phenotypes for gene: U2AF2 were set to Epilepsy; Developmental Delay; Intellectual Disability
Review for gene: U2AF2 was set to RED
Added comment: Novel gene. De novo variant identified in a child with epilepsy, global developmental delay and dysmorphism (Hiraide et al, J Hum Genetics 2021)
Sources: Expert list, Literature
Genetic Epilepsy v0.1263 UMPS Zornitza Stark Marked gene: UMPS as ready
Genetic Epilepsy v0.1263 UMPS Zornitza Stark Gene: umps has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1263 UMPS Zornitza Stark Classified gene: UMPS as Green List (high evidence)
Genetic Epilepsy v0.1263 UMPS Zornitza Stark Gene: umps has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v1.59 DLG4 Zornitza Stark Phenotypes for gene: DLG4 were changed from Intellectual developmental disorder 62, MIM#618793 to Intellectual developmental disorder 62, MIM#618793; Marfanoid features
Aortopathy_Connective Tissue Disorders v1.58 DLG4 Zornitza Stark edited their review of gene: DLG4: Changed phenotypes: Intellectual developmental disorder 62, MIM#618793, Marfanoid features
Aortopathy_Connective Tissue Disorders v1.58 DLG4 Zornitza Stark Marked gene: DLG4 as ready
Aortopathy_Connective Tissue Disorders v1.58 DLG4 Zornitza Stark Gene: dlg4 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v1.58 DLG4 Zornitza Stark Mode of inheritance for gene: DLG4 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v1.57 DLG4 Zornitza Stark Publications for gene: DLG4 were set to PMID: 33597769
Aortopathy_Connective Tissue Disorders v1.56 DLG4 Zornitza Stark Classified gene: DLG4 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v1.56 DLG4 Zornitza Stark Gene: dlg4 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v1.55 DLG4 Zornitza Stark changed review comment from: Marfanoid habits described in multiple affected individuals.; to: Marfanoid habitus described in multiple affected individuals.
Aortopathy_Connective Tissue Disorders v1.55 DLG4 Zornitza Stark reviewed gene: DLG4: Rating: GREEN; Mode of pathogenicity: None; Publications: 29460436; Phenotypes: Intellectual developmental disorder 62, MIM#618793; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1262 UMPS Krithika Murali gene: UMPS was added
gene: UMPS was added to Genetic Epilepsy. Sources: Expert list,Literature
Mode of inheritance for gene: UMPS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UMPS were set to 25757096; 33489760
Phenotypes for gene: UMPS were set to Orotic aciduria - 258900; Epilepsy
Review for gene: UMPS was set to GREEN
Added comment: Gene associated with orotic aciduria. Seizures have been reported in some individuals.
Sources: Expert list, Literature
Congenital nystagmus v0.0 MITF Zornitza Stark gene: MITF was added
gene: MITF was added to Albinism or congenital nystagmus. Sources: Expert Review Red,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: MITF was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: MITF were set to Waardenburg Syndrome Type 2 with Ocular Albinism (WS2-OA); Tietz Syndrome (TIETZS), Waardenburg Syndrome Type 2A (WS2A); Waardenburg syndrome/ocular albinism, digenic,103470
Congenital nystagmus v0.0 GNAI3 Zornitza Stark gene: GNAI3 was added
gene: GNAI3 was added to Albinism or congenital nystagmus. Sources: Expert Review Red,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: GNAI3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GNAI3 were set to 27607449
Phenotypes for gene: GNAI3 were set to Auriculocondylar syndrome 1 602483; Ocular Albinism
Congenital nystagmus v0.0 DGUOK Zornitza Stark gene: DGUOK was added
gene: DGUOK was added to Albinism or congenital nystagmus. Sources: Expert Review Red,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: DGUOK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DGUOK were set to 12210798; 12205643
Phenotypes for gene: DGUOK were set to Mitochondrial DNA depletion syndrome 3
Congenital nystagmus v0.0 TULP1 Zornitza Stark gene: TULP1 was added
gene: TULP1 was added to Albinism or congenital nystagmus. Sources: Expert Review Amber,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: TULP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TULP1 were set to Retinitis pigmentosa 14 600132 AR; Leber congenital amaurosis 15 613843 AR
Congenital nystagmus v0.0 MYO5A Zornitza Stark gene: MYO5A was added
gene: MYO5A was added to Albinism or congenital nystagmus. Sources: Expert Review Amber,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: MYO5A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MYO5A were set to Griscelli syndrome, type 1 214450 AR
Congenital nystagmus v0.0 MLPH Zornitza Stark gene: MLPH was added
gene: MLPH was added to Albinism or congenital nystagmus. Sources: Expert Review Amber,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: MLPH was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MLPH were set to Griscelli syndrome, type 3 609227 AR
Congenital nystagmus v0.0 MANBA Zornitza Stark gene: MANBA was added
gene: MANBA was added to Albinism or congenital nystagmus. Sources: Expert Review Amber,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: MANBA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MANBA were set to Mannosidosis, beta 248510 AR
Congenital nystagmus v0.0 LAMA1 Zornitza Stark gene: LAMA1 was added
gene: LAMA1 was added to Albinism or congenital nystagmus. Sources: Expert Review Amber,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: LAMA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LAMA1 were set to 29167897; 28283601; 32195884; 25105227; 328840387; 33251915
Phenotypes for gene: LAMA1 were set to Poretti-Boltshauser syndrome, OMIM:615960
Congenital nystagmus v0.0 DTNBP1 Zornitza Stark gene: DTNBP1 was added
gene: DTNBP1 was added to Albinism or congenital nystagmus. Sources: Expert Review Amber,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: DTNBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DTNBP1 were set to Hermansky-Pudlak syndrome 7 614076 AR
Congenital nystagmus v0.0 DCT Zornitza Stark gene: DCT was added
gene: DCT was added to Albinism or congenital nystagmus. Sources: Expert Review Amber,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: DCT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DCT were set to 33100333
Phenotypes for gene: DCT were set to Ocutaneous albinism
Congenital nystagmus v0.0 BLOC1S6 Zornitza Stark gene: BLOC1S6 was added
gene: BLOC1S6 was added to Albinism or congenital nystagmus. Sources: Expert Review Amber,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: BLOC1S6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: BLOC1S6 were set to ?Hermansky-pudlak syndrome 9 614171 AR
Congenital nystagmus v0.0 BLOC1S5 Zornitza Stark gene: BLOC1S5 was added
gene: BLOC1S5 was added to Albinism or congenital nystagmus. Sources: Expert Review Amber,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: BLOC1S5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BLOC1S5 were set to 32565547
Phenotypes for gene: BLOC1S5 were set to Hermansky-Pudlak syndrome, MONDO:0019312
Congenital nystagmus v0.0 BLOC1S3 Zornitza Stark gene: BLOC1S3 was added
gene: BLOC1S3 was added to Albinism or congenital nystagmus. Sources: Expert Review Amber,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: BLOC1S3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BLOC1S3 were set to 16385460; 32687635; 22709368
Phenotypes for gene: BLOC1S3 were set to Hermansky-Pudlak syndrome 8, OMIM:614077, MONDO:0013560
Congenital nystagmus v0.0 AP3D1 Zornitza Stark gene: AP3D1 was added
gene: AP3D1 was added to Albinism or congenital nystagmus. Sources: Expert Review Amber,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: AP3D1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: AP3D1 were set to ?Hermansky-Pudlak syndrome 10 617050 AR
Congenital nystagmus v0.0 AHR Zornitza Stark gene: AHR was added
gene: AHR was added to Albinism or congenital nystagmus. Sources: Expert Review Amber,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: AHR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AHR were set to 28851966; 31009037; 23301081
Phenotypes for gene: AHR were set to Foveal hypoplasia without albinism; ?Retinitis pigmentosa 85, 618345; Infantile nystagmus
Congenital nystagmus v0.0 TYRP1 Zornitza Stark gene: TYRP1 was added
gene: TYRP1 was added to Albinism or congenital nystagmus. Sources: Expert Review Green,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: TYRP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TYRP1 were set to Oculocutaneous Albinism; Albinism, oculocutaneous, type III
Congenital nystagmus v0.0 TYR Zornitza Stark gene: TYR was added
gene: TYR was added to Albinism or congenital nystagmus. Sources: Expert Review Green,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: TYR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: TYR were set to Albinism, oculocutaneous, type IA; Waardenburg syndrome/albinism, digenic; Oculocutaneous Albinism; Albinism, oculocutaneous, type IB
Congenital nystagmus v0.0 SLC45A2 Zornitza Stark gene: SLC45A2 was added
gene: SLC45A2 was added to Albinism or congenital nystagmus. Sources: Expert Review Green,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: SLC45A2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC45A2 were set to Oculocutaneous Albinism; Oculocutaneous albinism type IV,606574; skin/hair/eye pigmentation 5,227240; Albinism, oculocutaneous, type IV
Congenital nystagmus v0.0 SLC38A8 Zornitza Stark gene: SLC38A8 was added
gene: SLC38A8 was added to Albinism or congenital nystagmus. Sources: Expert Review Green,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: SLC38A8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC38A8 were set to 32744312; 24045842; 29345414; 24290379
Phenotypes for gene: SLC38A8 were set to foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome MONDO:0012216; Foveal hypoplasia 2, with or without optic nerve misrouting and/or anterior segment dysgenesis OMIM:609218
Congenital nystagmus v0.0 SLC24A5 Zornitza Stark gene: SLC24A5 was added
gene: SLC24A5 was added to Albinism or congenital nystagmus. Sources: Expert Review Green,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: SLC24A5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC24A5 were set to 23364476 - case report of patient of Chinese origin; 23985994 - homozygous variants identified in an additional 5 patients with Non-Syndromic Oculocutaneous Albinism; 26686029 case identified in a cohort South-Italian origin; 27129268 - functional data to support the phenotypic effects of variants reported
Phenotypes for gene: SLC24A5 were set to Non-Syndromic Oculocutaneous Albinism; Albinism, oculocutaneous, type VI
Congenital nystagmus v0.0 SETX Zornitza Stark gene: SETX was added
gene: SETX was added to Albinism or congenital nystagmus. Sources: Expert Review Green,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: SETX was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: SETX were set to Amyotrophic lateral sclerosis 4, juvenile 602433 AD; Spinocerebellar ataxia, autosomal recessive 1 606002 AR
Congenital nystagmus v0.0 SACS Zornitza Stark gene: SACS was added
gene: SACS was added to Albinism or congenital nystagmus. Sources: Expert Review Green,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: SACS was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SACS were set to Spastic ataxia, Charlevoix-Saguenay type 270550 AR
Congenital nystagmus v0.0 RAB27A Zornitza Stark gene: RAB27A was added
gene: RAB27A was added to Albinism or congenital nystagmus. Sources: Expert Review Green,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: RAB27A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RAB27A were set to Griscelli syndrome, type 2 607624 AR
Congenital nystagmus v0.0 PAX6 Zornitza Stark gene: PAX6 was added
gene: PAX6 was added to Albinism or congenital nystagmus. Sources: Expert Review Green,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: PAX6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: PAX6 were set to Aniridia 106210 AD; ?Coloboma of optic nerve 120430 AD; ?Morning glory disc anomaly 120430 AD; ?Coloboma, ocular 120200 AD; Anterior segment dysgenesis 5, multiple subtypes 604229; Keratitis 148190 AD; Optic nerve hypoplasia 165550 AD; Cataract with late-onset corneal dystrophy 106210 AD; Foveal hypoplasia 1 136520 AD
Congenital nystagmus v0.0 OCA2 Zornitza Stark gene: OCA2 was added
gene: OCA2 was added to Albinism or congenital nystagmus. Sources: Expert Review Green,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: OCA2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: OCA2 were set to Skin/hair/eye pigmentation 1, blond/brown hair; Albinism, oculocutaneous, type II; Oculocutaneous Albinism; Skin/hair/eye pigmentation 1, blue/nonblue eyes; Albinism, brown oculocutaneous
Congenital nystagmus v0.0 LYST Zornitza Stark gene: LYST was added
gene: LYST was added to Albinism or congenital nystagmus. Sources: Expert Review Green,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: LYST was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LYST were set to 20301751 - Chediak-Higashi syndrome (CHS) is characterized by partial oculocutaneous albinism (OCA), immunodeficiency, and a mild bleeding tendency.; 9215679; 10482950; 8896560
Phenotypes for gene: LYST were set to optic neuropathy with progressive vision loss; Chediak-Higashi syndrome; oculo-cutaneous albinism
Congenital nystagmus v0.0 LRMDA Zornitza Stark gene: LRMDA was added
gene: LRMDA was added to Albinism or congenital nystagmus. Sources: Expert Review Green,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: LRMDA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRMDA were set to PMID: 26818737 - a novel homozygous variant in this gene is reported a patient within a screen of Iranian patients with nonsyndromic OCA or autosomal recessive ocular albinism; PMID: 27031267 - identification of a 1.77-Mb de novo interstitial deletion in 10q22.2q22.3 in a female patient with 2.5-year-old female patient with developmental delay, speech delay, congenital cleft palate, and bilateral hearing impairment. The deletion included 9 genes, including KAT6B, DUPD1, DUSP13, SAMD8, VDAC2, COMTD1, ZNF503, NCRNA00245, and C10orf11; 23395477
Phenotypes for gene: LRMDA were set to Albinism, oculocutaneous, type VII
Congenital nystagmus v0.0 HPS6 Zornitza Stark gene: HPS6 was added
gene: HPS6 was added to Albinism or congenital nystagmus. Sources: Expert Review Green,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: HPS6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HPS6 were set to Hermansky-Pudlak syndrome 6 614075 AR
Congenital nystagmus v0.0 HPS5 Zornitza Stark gene: HPS5 was added
gene: HPS5 was added to Albinism or congenital nystagmus. Sources: Expert Review Green,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: HPS5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HPS5 were set to 12548288; 18182080; 27593200; 26785811; 28296950
Phenotypes for gene: HPS5 were set to Hermansky-Pudlak syndrome 5
Congenital nystagmus v0.0 HPS4 Zornitza Stark gene: HPS4 was added
gene: HPS4 was added to Albinism or congenital nystagmus. Sources: Expert Review Green,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: HPS4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HPS4 were set to 11836498; 15108212
Phenotypes for gene: HPS4 were set to Hermansky-Pudlak syndrome 4
Congenital nystagmus v0.0 HPS3 Zornitza Stark gene: HPS3 was added
gene: HPS3 was added to Albinism or congenital nystagmus. Sources: Expert Review Green,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: HPS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HPS3 were set to 11455388; 11590544
Phenotypes for gene: HPS3 were set to Hermansky-Pudlak syndrome 3
Congenital nystagmus v0.0 HPS1 Zornitza Stark gene: HPS1 was added
gene: HPS1 was added to Albinism or congenital nystagmus. Sources: Expert Review Green,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: HPS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HPS1 were set to 9705234; 10971344; 9497254; 7573033
Phenotypes for gene: HPS1 were set to Hermansky-Pudlak syndrome 1
Congenital nystagmus v0.0 GPR143 Zornitza Stark gene: GPR143 was added
gene: GPR143 was added to Albinism or congenital nystagmus. Sources: Expert Review Green,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: GPR143 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: GPR143 were set to 21541274; 26061757; 26160353; 21423867
Phenotypes for gene: GPR143 were set to Ocular albinism, type I; Nystagmus 6, congenital, X-linked, 300814; Ocular albinism, type I, Nettleship-Falls type, 300500
Congenital nystagmus v0.0 FRMD7 Zornitza Stark gene: FRMD7 was added
gene: FRMD7 was added to Albinism or congenital nystagmus. Sources: Expert Review Green,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: FRMD7 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: FRMD7 were set to 17013395; 17397053; 18431453; 17846367; 21303855; 24688117
Phenotypes for gene: FRMD7 were set to Nystagmus 1, Congenital, X-Linked; Nystagmus 1, congenital, X-linked, 310700; Infantile Nystagmus; (not relevant if inheritance through paternal line); Nystagmus, infantile periodic alternating, X-linked, 310700
Congenital nystagmus v0.0 CASK Zornitza Stark gene: CASK was added
gene: CASK was added to Albinism or congenital nystagmus. Sources: Expert Review Green,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: CASK was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: CASK were set to Mental retardation, with or without nystagmus 300422; FG syndrome 4 300422; Mental retardation and microcephaly with pontine and cerebellar hypoplasia 300749 XLD
Congenital nystagmus v0.0 CACNA1F Zornitza Stark gene: CACNA1F was added
gene: CACNA1F was added to Albinism or congenital nystagmus. Sources: Expert Review Green,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: CACNA1F was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: CACNA1F were set to Cone-rod dystrophy, X-linked, 3 300476 XLR; Aland Island eye disease 300600 XL; Night blindness, congenital stationary (incomplete), 2A, X-linked 300071 XL
Congenital nystagmus v0.0 CACNA1A Zornitza Stark gene: CACNA1A was added
gene: CACNA1A was added to Albinism or congenital nystagmus. Sources: Expert Review Green,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: CACNA1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CACNA1A were set to 19182766
Phenotypes for gene: CACNA1A were set to Acetazolamide-Responsive Hereditary Paroxysmal Cerebellar Ataxia; CACNA1A-Related Episodic Ataxia Type 2; Episodic Ataxia Type 2 (EA2) Episodic Ataxia, Nystagmus-Associated
Congenital nystagmus v0.0 AP3B1 Zornitza Stark gene: AP3B1 was added
gene: AP3B1 was added to Albinism or congenital nystagmus. Sources: Expert Review Green,NHS Genomic Medicine Service,Genomics England PanelApp
Mode of inheritance for gene: AP3B1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: AP3B1 were set to Hermansky-Pudlak syndrome 2 608233 AR
Congenital nystagmus v0.0 Zornitza Stark Added panel Albinism or congenital nystagmus
Aortopathy_Connective Tissue Disorders v1.55 DLG4 Elena Savva gene: DLG4 was added
gene: DLG4 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: DLG4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DLG4 were set to PMID: 33597769
Phenotypes for gene: DLG4 were set to Intellectual developmental disorder 62, MIM#618793
Review for gene: DLG4 was set to GREEN
Added comment: PMID: 33597769 - joint laxity reported in 13/38 patients, most patient variants were de novo PTCs
Sources: Literature
Mendeliome v0.9332 HNRNPD Zornitza Stark Phenotypes for gene: HNRNPD were changed from Developmental disorders to Neurodevelopmental disorder
Mendeliome v0.9331 HNRNPD Zornitza Stark Publications for gene: HNRNPD were set to 33057194
Mendeliome v0.9330 HNRNPD Zornitza Stark Classified gene: HNRNPD as Green List (high evidence)
Mendeliome v0.9330 HNRNPD Zornitza Stark Gene: hnrnpd has been classified as Green List (High Evidence).
Mendeliome v0.9329 HNRNPD Zornitza Stark reviewed gene: HNRNPD: Rating: GREEN; Mode of pathogenicity: None; Publications: 33874999; Phenotypes: Neurodevelopmental disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4183 HNRNPD Zornitza Stark Publications for gene: HNRNPD were set to 33057194
Intellectual disability syndromic and non-syndromic v0.4182 HNRNPD Zornitza Stark Phenotypes for gene: HNRNPD were changed from Developmental disorders to Neurodevelopmental disorder
Intellectual disability syndromic and non-syndromic v0.4181 HNRNPD Zornitza Stark Classified gene: HNRNPD as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4181 HNRNPD Zornitza Stark Gene: hnrnpd has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4180 HNRNPD Ee Ming Wong reviewed gene: HNRNPD: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33874999; Phenotypes: Neurodevelopmental disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.9329 EHHADH Zornitza Stark Mode of inheritance for gene: EHHADH was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9328 UNC13B Zornitza Stark Marked gene: UNC13B as ready
Mendeliome v0.9328 UNC13B Zornitza Stark Gene: unc13b has been classified as Red List (Low Evidence).
Mendeliome v0.9328 UNC13B Zornitza Stark gene: UNC13B was added
gene: UNC13B was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: UNC13B was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: UNC13B were set to 33876820
Phenotypes for gene: UNC13B were set to Epilepsy
Review for gene: UNC13B was set to RED
Added comment: No OMIM human disease association. Gene encodes a presynaptic protein Munc13-2 highly expressed in the brain (predominantly cerebral cortex).

Variant interpretation data in human epilepsy cohort somewhat conflicting and restricted to a single study. Conflicting data esp regarding MOI, and evidence for pathogenicity of several of the variants is limited.

Wang et al, Brain, 2021 - trio-based whole-exome sequencing identified UNC13B in 12 individuals affected by partial epilepsy and/or febrile seizures from 8 unrelated families. Identified:
x1 de novo nonsense variant, absent in gnomad, damaging in silicos
x1 de novo splice site, absent in gnomad, damaging in silicos
x1 splice site variant present in unaffected mother (low frequency in gnomad)
x2 compound het in one individual - more severe phenotype postulated (x1 variant present in contro cohortl, the other variant present in low frequency in gnomad)
x1 missense variant - in Han Chinese major depressive disorders study, not in gnomad
x1 missense variant - highly conserved residue, not in gnomad
x2 other missense variant - highly conserved residue, low frequency in gnomad
Latter 4 missense variants cosegregated with affected individuals in the families

In Drosophila, seizure rate and duration were increased by Unc13b knockdown compared to wild-type flies, but these effects were less pronounced than in sodium voltage-gated channel alpha subunit 1 (Scn1a) knockdown Drosophila

De novo UNC13B variants previously reported in bipolar disorder and autism spectrum disorder
Sources: Expert Review
Genetic Epilepsy v0.1262 UNC13B Zornitza Stark edited their review of gene: UNC13B: Changed rating: RED
Genetic Epilepsy v0.1262 UNC13B Zornitza Stark Mode of inheritance for gene: UNC13B was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.1261 UNC13B Zornitza Stark Marked gene: UNC13B as ready
Genetic Epilepsy v0.1261 UNC13B Zornitza Stark Added comment: Comment when marking as ready: Agree data is conflicting esp regarding MOI, and evidence for pathogenicity of several of the variants is limited.
Genetic Epilepsy v0.1261 UNC13B Zornitza Stark Gene: unc13b has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1261 UNC13B Zornitza Stark Classified gene: UNC13B as Red List (low evidence)
Genetic Epilepsy v0.1261 UNC13B Zornitza Stark Gene: unc13b has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1260 UNC13B Krithika Murali changed review comment from: No OMIM human disease association. Gene encodes a presynaptic protein Munc13-2 highly expressed in the brain (predominantly cerebral cortex).

Variant interpretation data in human epilepsy cohort somewhat conflicting and restricted to a single study. Wang et al, Brain, 2021 - trio-based whole-exome sequencing identified UNC13B in 12 individuals affected by partial epilepsy and/or febrile seizures from 8 unrelated families. Identified:
x1 de novo nonsense variant, absent in gnomad, damaging in silicos
x1 de novo splice site, absent in gnomad, damaging in silicos
x1 de novo splice site in unaffected mother (low frequency in gnomad)
x2 compound het in one individual - more severe phenotype postulated (x1 variant present in contro cohortl, the other variant present in low frequency in gnomad)
x1 missense variant - in Han Chinese major depressive disorders study, not in gnomad
x1 missense variant - highly conserved residue, not in gnomad
x2 other missense variant - highly conserved residue, low frequency in gnomad
Latter 4 missense variants cosegregated with affected individuals in the families

In Drosophila, seizure rate and duration were increased by Unc13b knockdown compared to wild-type flies, but these effects were less pronounced than in sodium voltage-gated channel alpha subunit 1 (Scn1a) knockdown Drosophila

De novo UNC13B variants previously reported in bipolar disorder and autism spectrum disorder
Sources: Expert list, Literature; to: No OMIM human disease association. Gene encodes a presynaptic protein Munc13-2 highly expressed in the brain (predominantly cerebral cortex).

Variant interpretation data in human epilepsy cohort somewhat conflicting and restricted to a single study. Wang et al, Brain, 2021 - trio-based whole-exome sequencing identified UNC13B in 12 individuals affected by partial epilepsy and/or febrile seizures from 8 unrelated families. Identified:
x1 de novo nonsense variant, absent in gnomad, damaging in silicos
x1 de novo splice site, absent in gnomad, damaging in silicos
x1 splice site variant present in unaffected mother (low frequency in gnomad)
x2 compound het in one individual - more severe phenotype postulated (x1 variant present in contro cohortl, the other variant present in low frequency in gnomad)
x1 missense variant - in Han Chinese major depressive disorders study, not in gnomad
x1 missense variant - highly conserved residue, not in gnomad
x2 other missense variant - highly conserved residue, low frequency in gnomad
Latter 4 missense variants cosegregated with affected individuals in the families

In Drosophila, seizure rate and duration were increased by Unc13b knockdown compared to wild-type flies, but these effects were less pronounced than in sodium voltage-gated channel alpha subunit 1 (Scn1a) knockdown Drosophila

De novo UNC13B variants previously reported in bipolar disorder and autism spectrum disorder
Sources: Expert list, Literature
Genetic Epilepsy v0.1260 UNC13B Krithika Murali gene: UNC13B was added
gene: UNC13B was added to Genetic Epilepsy. Sources: Expert list,Literature
Mode of inheritance for gene: UNC13B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UNC13B were set to 33876820
Phenotypes for gene: UNC13B were set to Epilepsy
Penetrance for gene: UNC13B were set to unknown
Review for gene: UNC13B was set to RED
Added comment: No OMIM human disease association. Gene encodes a presynaptic protein Munc13-2 highly expressed in the brain (predominantly cerebral cortex).

Variant interpretation data in human epilepsy cohort somewhat conflicting and restricted to a single study. Wang et al, Brain, 2021 - trio-based whole-exome sequencing identified UNC13B in 12 individuals affected by partial epilepsy and/or febrile seizures from 8 unrelated families. Identified:
x1 de novo nonsense variant, absent in gnomad, damaging in silicos
x1 de novo splice site, absent in gnomad, damaging in silicos
x1 de novo splice site in unaffected mother (low frequency in gnomad)
x2 compound het in one individual - more severe phenotype postulated (x1 variant present in contro cohortl, the other variant present in low frequency in gnomad)
x1 missense variant - in Han Chinese major depressive disorders study, not in gnomad
x1 missense variant - highly conserved residue, not in gnomad
x2 other missense variant - highly conserved residue, low frequency in gnomad
Latter 4 missense variants cosegregated with affected individuals in the families

In Drosophila, seizure rate and duration were increased by Unc13b knockdown compared to wild-type flies, but these effects were less pronounced than in sodium voltage-gated channel alpha subunit 1 (Scn1a) knockdown Drosophila

De novo UNC13B variants previously reported in bipolar disorder and autism spectrum disorder
Sources: Expert list, Literature
Mitochondrial disease v0.651 VARS2 Zornitza Stark Marked gene: VARS2 as ready
Mitochondrial disease v0.651 VARS2 Zornitza Stark Gene: vars2 has been classified as Green List (High Evidence).
Mitochondrial disease v0.651 VARS2 Zornitza Stark Phenotypes for gene: VARS2 were changed from to Combined oxidative phosphorylation deficiency 20; OMIM #615917
Mitochondrial disease v0.650 VARS2 Zornitza Stark Publications for gene: VARS2 were set to
Mitochondrial disease v0.649 VARS2 Zornitza Stark Mode of inheritance for gene: VARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.648 VARS2 Zornitza Stark reviewed gene: VARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24827421, 25058219, 29137650, 29314548, 31064326, 31623496; Phenotypes: Combined oxidative phosphorylation deficiency 20, OMIM #615917; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9327 VARS2 Zornitza Stark Marked gene: VARS2 as ready
Mendeliome v0.9327 VARS2 Zornitza Stark Gene: vars2 has been classified as Green List (High Evidence).
Mendeliome v0.9327 VARS2 Zornitza Stark Phenotypes for gene: VARS2 were changed from to Combined oxidative phosphorylation deficiency 20; OMIM #615917
Mendeliome v0.9326 VARS2 Zornitza Stark Publications for gene: VARS2 were set to
Mendeliome v0.9325 VARS2 Zornitza Stark Mode of inheritance for gene: VARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9324 VARS2 Zornitza Stark reviewed gene: VARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24827421, 25058219, 29137650, 29314548, 31064326, 31623496; Phenotypes: Combined oxidative phosphorylation deficiency 20, OMIM #615917; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1260 VARS2 Zornitza Stark Marked gene: VARS2 as ready
Genetic Epilepsy v0.1260 VARS2 Zornitza Stark Gene: vars2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1260 VARS2 Zornitza Stark Classified gene: VARS2 as Green List (high evidence)
Genetic Epilepsy v0.1260 VARS2 Zornitza Stark Gene: vars2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1259 VARS2 Krithika Murali gene: VARS2 was added
gene: VARS2 was added to Genetic Epilepsy. Sources: Expert list,Literature
Mode of inheritance for gene: VARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VARS2 were set to 27502409; 29137650; 31064326; 31623496
Phenotypes for gene: VARS2 were set to Combined oxidative phosphorylation deficiency 20, 615917; Epilepsy
Review for gene: VARS2 was set to GREEN
Added comment: Established gene associated with mitochondrial disorder. Heterogeneous clinical features reported including seizures, epilepsy, encephalopathy, microcephaly, global developmental delay, hypotonia, ataxia, dystonic movements, limb spasticity, hypertrophic cardiomyopathy, hyperlactaemia and MRI-B abnormalities.
Sources: Expert list, Literature
Genetic Epilepsy v0.1259 ZDHHC15 Zornitza Stark Marked gene: ZDHHC15 as ready
Genetic Epilepsy v0.1259 ZDHHC15 Zornitza Stark Gene: zdhhc15 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1259 ZDHHC15 Zornitza Stark Classified gene: ZDHHC15 as Red List (low evidence)
Genetic Epilepsy v0.1259 ZDHHC15 Zornitza Stark Gene: zdhhc15 has been classified as Red List (Low Evidence).
Mendeliome v0.9324 CHD4 Zornitza Stark Phenotypes for gene: CHD4 were changed from Sifrim-Hitz-Weiss syndrome, MIM 617159 to Sifrim-Hitz-Weiss syndrome, MIM 617159; Childhood idiopathic epilepsy and sinus arrhythmia
Mendeliome v0.9323 CHD4 Zornitza Stark Publications for gene: CHD4 were set to 31388190
Mendeliome v0.9322 CHD4 Zornitza Stark reviewed gene: CHD4: Rating: GREEN; Mode of pathogenicity: None; Publications: 34109749; Phenotypes: Childhood idiopathic epilepsy and sinus arrhythmia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1258 CHD4 Zornitza Stark Phenotypes for gene: CHD4 were changed from Sifrim-Hitz-Weiss syndrome, MIM# 617159 to Sifrim-Hitz-Weiss syndrome, MIM# 617159; Childhood idiopathic epilepsy and sinus arrhythmia
Genetic Epilepsy v0.1257 CHD4 Zornitza Stark Publications for gene: CHD4 were set to 27479907; 27616479
Genetic Epilepsy v0.1256 CHD4 Zornitza Stark Classified gene: CHD4 as Green List (high evidence)
Genetic Epilepsy v0.1256 CHD4 Zornitza Stark Gene: chd4 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1255 CHD4 Zornitza Stark edited their review of gene: CHD4: Added comment: New publication, PMID 34109749: 8 individuals from 4 families with childhood idiopathic epilepsy and sinus arrhythmia. This may be a distinct gene-disease association as the variants were located outside of the typical domains associated with SHW syndrome (central regions from SNF2-like region to DUF1087 domain).; Changed rating: GREEN; Changed publications: 27479907, 27616479, 34109749; Changed phenotypes: Sifrim-Hitz-Weiss syndrome, MIM# 617159, Childhood idiopathic epilepsy and sinus arrhythmia
Genetic Epilepsy v0.1255 CCM2 Zornitza Stark Marked gene: CCM2 as ready
Genetic Epilepsy v0.1255 CCM2 Zornitza Stark Gene: ccm2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1255 CCM2 Zornitza Stark gene: CCM2 was added
gene: CCM2 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: CCM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCM2 were set to 32702807
Phenotypes for gene: CCM2 were set to Cerebral cavernous malformations-2, MIM#603284
Review for gene: CCM2 was set to RED
Added comment: Rare reports of presentation with seizures following bleeding.
Sources: Expert Review
Genetic Epilepsy v0.1254 CARS2 Zornitza Stark Marked gene: CARS2 as ready
Genetic Epilepsy v0.1254 CARS2 Zornitza Stark Gene: cars2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1254 CARS2 Zornitza Stark Classified gene: CARS2 as Green List (high evidence)
Genetic Epilepsy v0.1254 CARS2 Zornitza Stark Gene: cars2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1253 CARS2 Zornitza Stark gene: CARS2 was added
gene: CARS2 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: CARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CARS2 were set to 25361775; 25787132; 30139652
Phenotypes for gene: CARS2 were set to Combined oxidative phosphorylation deficiency 27, MIM# 616672
Review for gene: CARS2 was set to GREEN
Added comment: Three families reported with supportive functional data, epilepsy is a feature.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.4180 BPTF Zornitza Stark Publications for gene: BPTF were set to 28942966; 33522091
Intellectual disability syndromic and non-syndromic v0.4180 BPTF Zornitza Stark Publications for gene: BPTF were set to 28942966
Genetic Epilepsy v0.1252 BPTF Zornitza Stark Marked gene: BPTF as ready
Genetic Epilepsy v0.1252 BPTF Zornitza Stark Gene: bptf has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1252 BPTF Zornitza Stark Classified gene: BPTF as Green List (high evidence)
Genetic Epilepsy v0.1252 BPTF Zornitza Stark Gene: bptf has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4179 BPTF Zornitza Stark commented on gene: BPTF: Over 30 unrelated individuals reported, mostly de novo, some inherited variants. Clinical features include intellectual disability, seizures, poor growth with small head size, dysmorphic facial features, and mild abnormalities of the hands and feet.
Genetic Epilepsy v0.1251 BPTF Zornitza Stark gene: BPTF was added
gene: BPTF was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: BPTF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BPTF were set to 33522091; 28942966
Phenotypes for gene: BPTF were set to Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies AD, MIM#617755
Review for gene: BPTF was set to GREEN
Added comment: Over 30 individuals reported, mostly de novo, some inherited variants. Reported features include seizures.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4179 BPTF Zornitza Stark edited their review of gene: BPTF: Changed publications: 28942966, 33522091
Mendeliome v0.9322 BCL11A Zornitza Stark Marked gene: BCL11A as ready
Mendeliome v0.9322 BCL11A Zornitza Stark Gene: bcl11a has been classified as Green List (High Evidence).
Mendeliome v0.9322 BCL11A Zornitza Stark Phenotypes for gene: BCL11A were changed from to Dias-Logan syndrome, MIM# 617101
Mendeliome v0.9321 BCL11A Zornitza Stark Publications for gene: BCL11A were set to
Mendeliome v0.9320 BCL11A Zornitza Stark Mode of inheritance for gene: BCL11A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9319 BCL11A Zornitza Stark reviewed gene: BCL11A: Rating: GREEN; Mode of pathogenicity: None; Publications: 27453576, 32903878; Phenotypes: Dias-Logan syndrome, MIM# 617101; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4179 BCL11A Zornitza Stark Marked gene: BCL11A as ready
Intellectual disability syndromic and non-syndromic v0.4179 BCL11A Zornitza Stark Gene: bcl11a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4179 BCL11A Zornitza Stark Phenotypes for gene: BCL11A were changed from to Dias-Logan syndrome, MIM# 617101
Intellectual disability syndromic and non-syndromic v0.4178 BCL11A Zornitza Stark Publications for gene: BCL11A were set to
Genetic Epilepsy v0.1250 ZDHHC15 Krithika Murali gene: ZDHHC15 was added
gene: ZDHHC15 was added to Genetic Epilepsy. Sources: Expert list,Literature
Mode of inheritance for gene: ZDHHC15 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: ZDHHC15 were set to 34345675; 15915161; 26290131; 32989326
Phenotypes for gene: ZDHHC15 were set to Mental retardation X-linked 91, 300577; cerebral palsy; intellectual disability; autism spectrum disorder; epilepsy
Review for gene: ZDHHC15 was set to RED
Added comment: 1 reported case of an 18 yo M with hypotonic cerebral palsy, focal-onset epilepsy, cortical visual impairment, intellectual disability, autism spectrum disorder, anxiety, and aggressive behaviors with hemizygous p.H158R variant shown to affect protein function in yeast complementation assay (Lewis et al Neurology Genetics 2021 PMID 34345675).

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Other background info:

Protein function of x4 ZDHHC15 variants assessed by Lewis et al. x2 variants identified through Jin et al Nat Genet 2020 (PMID 32989326) - maternally inherited p.H158R and p.L13P. x1 identified through Gene Matcher p.S330P and x1 through GeneDx maternally inherited p.K115R. Only p.H158R variant shown to affect protein function. In Drosophilia model LoF variants caused flight and co-ordinated movement defects supporting role in motor dysfunction.

Conflicting evidence for ID phenotype

1 case with intellectual disability and balanced translocation with breakpoints near the ZDHHC15 gene - functional studies showing absence of ZDHHC15 transcript variants. This patient showed skewed lyonization, with 100% inactivation of the normal X chromosome. PMID: 15915161

1 case with NO intellectual disability and balanced translocation with breakpoints in the ZDHHC15 gene - functional studies showing no gene expression in the patient's peripheral blood (PMID 26290131)
Sources: Expert list, Literature
Intellectual disability syndromic and non-syndromic v0.4177 BCL11A Zornitza Stark Mode of inheritance for gene: BCL11A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4176 BCL11A Zornitza Stark reviewed gene: BCL11A: Rating: GREEN; Mode of pathogenicity: None; Publications: 27453576, 32903878; Phenotypes: Dias-Logan syndrome, MIM# 617101; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1250 BCL11A Zornitza Stark Marked gene: BCL11A as ready
Genetic Epilepsy v0.1250 BCL11A Zornitza Stark Gene: bcl11a has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1250 BCL11A Zornitza Stark gene: BCL11A was added
gene: BCL11A was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: BCL11A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BCL11A were set to 27453576; 32903878
Phenotypes for gene: BCL11A were set to Dias-Logan syndrome, MIM# 617101
Review for gene: BCL11A was set to RED
Added comment: Epilepsy appears to be a rare feature of this syndrome.
Sources: Expert Review
Mendeliome v0.9319 CFAP221 Zornitza Stark Marked gene: CFAP221 as ready
Mendeliome v0.9319 CFAP221 Zornitza Stark Gene: cfap221 has been classified as Red List (Low Evidence).
Mendeliome v0.9319 CFAP221 Zornitza Stark gene: CFAP221 was added
gene: CFAP221 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP221 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP221 were set to 31636325
Phenotypes for gene: CFAP221 were set to Primary ciliary dyskinesia
Review for gene: CFAP221 was set to RED
Added comment: WES in 1 family with 3 siblings with clinical symptoms of PCD identified compound heterozygous loss-of-function variants in CFAP221, which segregated with disease. No functional studies. Nasal epithelial cells from 1 of the subjects demonstrated slightly reduced beat frequency, however, waveform analysis revealed that the CFAP221 defective cilia beat in an aberrant circular pattern. A candidate gene in cases where PCD is suspected but cilia structure and beat frequency appear normal.
Sources: Literature
Ciliary Dyskinesia v1.13 CFAP221 Zornitza Stark Marked gene: CFAP221 as ready
Ciliary Dyskinesia v1.13 CFAP221 Zornitza Stark Gene: cfap221 has been classified as Red List (Low Evidence).
Ciliary Dyskinesia v1.13 CFAP221 Chirag Patel gene: CFAP221 was added
gene: CFAP221 was added to Ciliary Dyskinesia. Sources: Literature
Mode of inheritance for gene: CFAP221 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP221 were set to PMID: 31636325
Phenotypes for gene: CFAP221 were set to Primary ciliary dyskinesia
Review for gene: CFAP221 was set to RED
Added comment: WES in 1 family with 3 siblings with clinical symptoms of PCD identified compound heterozygous loss-of-function variants in CFAP221, which segregated with disease. No functional studies. Nasal epithelial cells from 1 of the subjects demonstrated slightly reduced beat frequency, however, waveform analysis revealed that the CFAP221 defective cilia beat in an aberrant circular pattern. A candidate gene in cases where PCD is suspected but cilia structure and beat frequency appear normal.
Sources: Literature
Mendeliome v0.9318 DAB1 Zornitza Stark Mode of inheritance for gene: DAB1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9317 DAB1 Zornitza Stark Phenotypes for gene: DAB1 were changed from to Spinocerebellar ataxia 37 MIM#615945; Ataxia and intellectual disability
Mendeliome v0.9316 DAB1 Zornitza Stark Publications for gene: DAB1 were set to
Mendeliome v0.9315 DAB1 Zornitza Stark Mode of pathogenicity for gene: DAB1 was changed from to None
Mendeliome v0.9314 DAB1 Zornitza Stark Mode of inheritance for gene: DAB1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9313 DAB1 Zornitza Stark Classified gene: DAB1 as Red List (low evidence)
Mendeliome v0.9313 DAB1 Zornitza Stark Gene: dab1 has been classified as Red List (Low Evidence).
Mendeliome v0.9312 DAB1 Zornitza Stark reviewed gene: DAB1: Rating: RED; Mode of pathogenicity: None; Publications: 33928188; Phenotypes: Ataxia, Intellectual disability; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia v0.293 DAB1 Zornitza Stark Marked gene: DAB1 as ready
Ataxia v0.293 DAB1 Zornitza Stark Gene: dab1 has been classified as Red List (Low Evidence).
Ataxia v0.293 DAB1 Zornitza Stark Classified gene: DAB1 as Red List (low evidence)
Ataxia v0.293 DAB1 Zornitza Stark Gene: dab1 has been classified as Red List (Low Evidence).
Ataxia v0.292 DAB1 Zornitza Stark reviewed gene: DAB1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ataxia, Intellectual disability; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4176 SNIP1 Zornitza Stark Publications for gene: SNIP1 were set to 22279524
Intellectual disability syndromic and non-syndromic v0.4175 SNIP1 Zornitza Stark changed review comment from: Three Amish individuals with same homozygous variant, founder effect.; to: Four Amish individuals with same homozygous variant, founder effect.
Intellectual disability syndromic and non-syndromic v0.4175 SNIP1 Zornitza Stark edited their review of gene: SNIP1: Changed publications: 22279524, 34570759
Callosome v0.327 SNIP1 Zornitza Stark Publications for gene: SNIP1 were set to 22279524
Callosome v0.326 SNIP1 Zornitza Stark Tag founder tag was added to gene: SNIP1.
Callosome v0.326 SNIP1 Zornitza Stark changed review comment from: Three Amish individuals with same homozygous variant, founder effect.; to: Four Amish individuals with same homozygous variant, founder effect.
Callosome v0.326 SNIP1 Zornitza Stark edited their review of gene: SNIP1: Changed publications: 22279524, 34570759
Mendeliome v0.9312 SNIP1 Zornitza Stark Tag founder tag was added to gene: SNIP1.
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.195 PANX1 Zornitza Stark changed review comment from: Two unrelated families, some functional data. However, clinical presentation is with infertility rather than POI/POF.; to: Two unrelated families with balletic variants, some functional data. Four with mono-allelic variants. However, clinical presentation is with infertility rather than POI/POF.
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.195 PANX1 Zornitza Stark edited their review of gene: PANX1: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9312 ERBB4 Zornitza Stark Marked gene: ERBB4 as ready
Mendeliome v0.9312 ERBB4 Zornitza Stark Gene: erbb4 has been classified as Green List (High Evidence).
Mendeliome v0.9312 ERBB4 Zornitza Stark Phenotypes for gene: ERBB4 were changed from to Amyotrophic lateral sclerosis 19, MIM# MIM#615515; Intellectual disability
Mendeliome v0.9311 ERBB4 Zornitza Stark Publications for gene: ERBB4 were set to
Mendeliome v0.9310 ERBB4 Zornitza Stark Mode of inheritance for gene: ERBB4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9309 ERBB4 Zornitza Stark reviewed gene: ERBB4: Rating: GREEN; Mode of pathogenicity: None; Publications: 24119685, 28889094, 33603162; Phenotypes: Amyotrophic lateral sclerosis 19, MIM# MIM#615515, Intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4175 LONP1 Zornitza Stark Marked gene: LONP1 as ready
Intellectual disability syndromic and non-syndromic v0.4175 LONP1 Zornitza Stark Gene: lonp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4175 ERBB4 Zornitza Stark Phenotypes for gene: ERBB4 were changed from to Intellectual disability
Intellectual disability syndromic and non-syndromic v0.4174 ERBB4 Zornitza Stark Tag SV/CNV tag was added to gene: ERBB4.
Leukodystrophy v0.236 ATP11A Zornitza Stark Phenotypes for gene: ATP11A were changed from PMID: 34403372 to Neurological disorder
Congenital Heart Defect v0.131 WLS Zornitza Stark Marked gene: WLS as ready
Congenital Heart Defect v0.131 WLS Zornitza Stark Gene: wls has been classified as Green List (High Evidence).
Congenital Heart Defect v0.131 WLS Zornitza Stark Classified gene: WLS as Green List (high evidence)
Congenital Heart Defect v0.131 WLS Zornitza Stark Gene: wls has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4174 LONP1 Zornitza Stark Phenotypes for gene: LONP1 were changed from CODAS syndrome, MIM#600373; Mitochondrial cytopathy to CODAS syndrome, MIM#600373; Mitochondrial cytopathy
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.89 WLS Zornitza Stark Marked gene: WLS as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.89 WLS Zornitza Stark Gene: wls has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4174 LONP1 Zornitza Stark Phenotypes for gene: LONP1 were changed from to CODAS syndrome, MIM#600373; Mitochondrial cytopathy
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.89 WLS Zornitza Stark Classified gene: WLS as Green List (high evidence)
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.89 WLS Zornitza Stark Gene: wls has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4173 LONP1 Zornitza Stark Publications for gene: LONP1 were set to
Anophthalmia_Microphthalmia_Coloboma v1.9 WLS Zornitza Stark Marked gene: WLS as ready
Anophthalmia_Microphthalmia_Coloboma v1.9 WLS Zornitza Stark Gene: wls has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4172 LONP1 Zornitza Stark Mode of inheritance for gene: LONP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4171 LONP1 Zornitza Stark reviewed gene: LONP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31636596; Phenotypes: CODAS syndrome, MIM#600373, Mitochondrial cytopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Anophthalmia_Microphthalmia_Coloboma v1.9 WLS Zornitza Stark Classified gene: WLS as Green List (high evidence)
Anophthalmia_Microphthalmia_Coloboma v1.9 WLS Zornitza Stark Gene: wls has been classified as Green List (High Evidence).
Microcephaly v1.60 WLS Zornitza Stark Marked gene: WLS as ready
Microcephaly v1.60 WLS Zornitza Stark Gene: wls has been classified as Green List (High Evidence).
Microcephaly v1.60 WLS Zornitza Stark Classified gene: WLS as Green List (high evidence)
Microcephaly v1.60 WLS Zornitza Stark Gene: wls has been classified as Green List (High Evidence).
Microcephaly v1.59 WLS Zornitza Stark Classified gene: WLS as Green List (high evidence)
Microcephaly v1.59 WLS Zornitza Stark Gene: wls has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4171 WIPI2 Zornitza Stark Phenotypes for gene: WIPI2 were changed from Intellectual developmental disorder with short stature and variable skeletal anomalies 618453 to Intellectual developmental disorder with short stature and variable skeletal anomalies 618453; global developmental delay; intellectual disability; refractory infantile/childhood-onset epilepsy; progressive tetraplegia with joint contractures; dyskinesia; speech and visual impairment; autistic features; ataxic gait
Intellectual disability syndromic and non-syndromic v0.4171 WIPI2 Zornitza Stark Publications for gene: WIPI2 were set to 30968111
Intellectual disability syndromic and non-syndromic v0.4170 WIPI2 Zornitza Stark Classified gene: WIPI2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4170 WIPI2 Zornitza Stark Gene: wipi2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4169 ZDHHC15 Zornitza Stark Phenotypes for gene: ZDHHC15 were changed from to Mental retardation, X-linked 91, 300577
Intellectual disability syndromic and non-syndromic v0.4168 ZDHHC15 Zornitza Stark Publications for gene: ZDHHC15 were set to
Intellectual disability syndromic and non-syndromic v0.4167 ZDHHC15 Zornitza Stark Mode of inheritance for gene: ZDHHC15 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.4166 ZDHHC15 Zornitza Stark reviewed gene: ZDHHC15: Rating: RED; Mode of pathogenicity: None; Publications: 34345675, 32989326; Phenotypes: Mental retardation, X-linked 91, 300577; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Ataxia v0.292 DAB1 Daniel Flanagan gene: DAB1 was added
gene: DAB1 was added to Ataxia - paediatric. Sources: Literature
Mode of inheritance for gene: DAB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DAB1 were set to PMID: 33928188
Phenotypes for gene: DAB1 were set to epilepsy; developmental delay; cerebellar ataxia; structural brain abnormalities; oral motor difficulty
Penetrance for gene: DAB1 were set to unknown
Review for gene: DAB1 was set to AMBER
Added comment: WES trio analysis identified compound heterozygous DAB1 canonical splice variants in a child with epilepsy (onset 6 years), developmental delay, cerebellar ataxia, oral motor difficulty, and structural brain abnormalities. RT-PCR confirms that the first variant (c.307-2A>T) causes a in-frame deletion of 3 amino acids. The second variant (c.67+1G>T) is reported to causes an in-frame deletion of exon 4 (first coding exon) and loss of the ATG initiation site.
Sources: Literature
Hereditary Spastic Paraplegia v1.18 ABHD16A Seb Lunke Marked gene: ABHD16A as ready
Hereditary Spastic Paraplegia v1.18 ABHD16A Seb Lunke Gene: abhd16a has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v1.18 ABHD16A Seb Lunke Classified gene: ABHD16A as Green List (high evidence)
Hereditary Spastic Paraplegia v1.18 ABHD16A Seb Lunke Gene: abhd16a has been classified as Green List (High Evidence).
Leukodystrophy v0.235 ABHD16A Seb Lunke Marked gene: ABHD16A as ready
Leukodystrophy v0.235 ABHD16A Seb Lunke Gene: abhd16a has been classified as Green List (High Evidence).
Leukodystrophy v0.235 ABHD16A Seb Lunke Phenotypes for gene: ABHD16A were changed from Spastic paraplegia to Spastic paraplegia; intellectual disability; callosome
Leukodystrophy v0.234 ABHD16A Seb Lunke Classified gene: ABHD16A as Green List (high evidence)
Leukodystrophy v0.234 ABHD16A Seb Lunke Gene: abhd16a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4166 ERBB4 Seb Lunke Marked gene: ERBB4 as ready
Intellectual disability syndromic and non-syndromic v0.4166 ERBB4 Seb Lunke Gene: erbb4 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4166 ERBB4 Seb Lunke Classified gene: ERBB4 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.4166 ERBB4 Seb Lunke Added comment: Comment on list classification: CNVs only, not clear on the differentiation between ID and ALS.
Intellectual disability syndromic and non-syndromic v0.4166 ERBB4 Seb Lunke Gene: erbb4 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4165 ABHD16A Seb Lunke Marked gene: ABHD16A as ready
Intellectual disability syndromic and non-syndromic v0.4165 ABHD16A Seb Lunke Gene: abhd16a has been classified as Green List (High Evidence).
Callosome v0.326 ABHD16A Seb Lunke Marked gene: ABHD16A as ready
Callosome v0.326 ABHD16A Seb Lunke Gene: abhd16a has been classified as Green List (High Evidence).
Leukodystrophy v0.233 ABHD16A Lucy Spencer edited their review of gene: ABHD16A: Changed phenotypes: Spastic paraplegia, intellectual disability, callosome
Leukodystrophy v0.233 ABHD16A Lucy Spencer changed review comment from: 11 individuals from 6 families with a complicated form of hereditary spastic paraplegia who carry bi-allelic deleterious variants in ABHD16A. Affected individuals present with a similar phenotype consisting of global developmental delay/intellectual disability, progressive spasticity affecting the upper and lower limbs, and corpus callosum and white matter anomalies. Immunoblot analysis on extracts from fibroblasts from four affected individuals demonstrated little to no ABHD16A protein levels compared to controls.
In 5 of the families the affected members were homozygous, 3 of these families were consanguineous. 2 families have the same variant- both families are French-Canadian.
4 missense variants, 1 frameshift, 1 nonsense.
From PMID: 34587489
Sources: Literature; to: 11 individuals from 6 families with a complicated form of hereditary spastic paraplegia who carry bi-allelic deleterious variants in ABHD16A. Affected individuals present with a similar phenotype consisting of global developmental delay/intellectual disability, progressive spasticity affecting the upper and lower limbs, and corpus callosum and white matter anomalies. Immunoblot analysis on extracts from fibroblasts from four affected individuals demonstrated little to no ABHD16A protein levels compared to controls.
In 5 of the families the affected members were homozygous, 3 of these families were consanguineous. 2 families have the same variant- both families are French-Canadian.
4 missense variants, 1 frameshift, 1 nonsense.
From PMID: 34587489
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4165 ABHD16A Seb Lunke Phenotypes for gene: ABHD16A were changed from Spastic paraplegia to Spastic paraplegia; Intellectual Disability; Callosome
Callosome v0.326 ABHD16A Seb Lunke Phenotypes for gene: ABHD16A were changed from Spastic paraplegia to Spastic paraplegia; Intellectual Disability; Callosome
Hereditary Spastic Paraplegia v1.17 ABHD16A Lucy Spencer gene: ABHD16A was added
gene: ABHD16A was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature
Mode of inheritance for gene: ABHD16A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABHD16A were set to PMID: 34587489
Phenotypes for gene: ABHD16A were set to Spastic paraplegia; intellectual disability; callosome
Review for gene: ABHD16A was set to GREEN
Added comment: 11 individuals from 6 families with a complicated form of hereditary spastic paraplegia who carry bi-allelic deleterious variants in ABHD16A. Affected individuals present with a similar phenotype consisting of global developmental delay/intellectual disability, progressive spasticity affecting the upper and lower limbs, and corpus callosum and white matter anomalies. Immunoblot analysis on extracts from fibroblasts from four affected individuals demonstrated little to no ABHD16A protein levels compared to controls.
In 5 of the families the affected members were homozygous, 3 of these families were consanguineous. 2 families have the same variant- both families are French-Canadian.
4 missense variants, 1 frameshift, 1 nonsense.
From PMID: 34587489
Sources: Literature
Mendeliome v0.9309 PANX1 Zornitza Stark Publications for gene: PANX1 were set to 30918116; 32838805
Intellectual disability syndromic and non-syndromic v0.4164 WIPI2 Dean Phelan reviewed gene: WIPI2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30968111, 34557665; Phenotypes: global developmental delay, intellectual disability, refractory infantile/childhood-onset epilepsy, progressive tetraplegia with joint contractures, dyskinesia, speech and visual impairment, autistic features, ataxic gait; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.4164 ABHD16A Seb Lunke Classified gene: ABHD16A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4164 ABHD16A Seb Lunke Gene: abhd16a has been classified as Green List (High Evidence).
Mendeliome v0.9308 PANX1 Zornitza Stark Mode of pathogenicity for gene: PANX1 was changed from None to Other
Callosome v0.325 ABHD16A Seb Lunke Classified gene: ABHD16A as Green List (high evidence)
Callosome v0.325 ABHD16A Seb Lunke Gene: abhd16a has been classified as Green List (High Evidence).
Mendeliome v0.9307 PANX1 Zornitza Stark Mode of inheritance for gene: PANX1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9306 PANX1 Zornitza Stark Classified gene: PANX1 as Green List (high evidence)
Mendeliome v0.9306 PANX1 Zornitza Stark Gene: panx1 has been classified as Green List (High Evidence).
Leukodystrophy v0.233 ABHD16A Lucy Spencer gene: ABHD16A was added
gene: ABHD16A was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: ABHD16A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABHD16A were set to PMID: 34587489
Phenotypes for gene: ABHD16A were set to Spastic paraplegia
Review for gene: ABHD16A was set to GREEN
Added comment: 11 individuals from 6 families with a complicated form of hereditary spastic paraplegia who carry bi-allelic deleterious variants in ABHD16A. Affected individuals present with a similar phenotype consisting of global developmental delay/intellectual disability, progressive spasticity affecting the upper and lower limbs, and corpus callosum and white matter anomalies. Immunoblot analysis on extracts from fibroblasts from four affected individuals demonstrated little to no ABHD16A protein levels compared to controls.
In 5 of the families the affected members were homozygous, 3 of these families were consanguineous. 2 families have the same variant- both families are French-Canadian.
4 missense variants, 1 frameshift, 1 nonsense.
From PMID: 34587489
Sources: Literature
Callosome v0.324 ABHD16A Lucy Spencer gene: ABHD16A was added
gene: ABHD16A was added to Callosome. Sources: Literature
Mode of inheritance for gene: ABHD16A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABHD16A were set to PMID: 34587489
Phenotypes for gene: ABHD16A were set to Spastic paraplegia
Review for gene: ABHD16A was set to GREEN
Added comment: 11 individuals from 6 families with a complicated form of hereditary spastic paraplegia who carry bi-allelic deleterious variants in ABHD16A. Affected individuals present with a similar phenotype consisting of global developmental delay/intellectual disability, progressive spasticity affecting the upper and lower limbs, and corpus callosum and white matter anomalies. Immunoblot analysis on extracts from fibroblasts from four affected individuals demonstrated little to no ABHD16A protein levels compared to controls.
In 5 of the families the affected members were homozygous, 3 of these families were consanguineous. 2 families have the same variant- both families are French-Canadian.
4 missense variants, 1 frameshift, 1 nonsense.
From PMID: 34587489
Sources: Literature
Mendeliome v0.9305 ZDHHC15 Zornitza Stark Phenotypes for gene: ZDHHC15 were changed from Mental retardation, X-linked 91, 300577 to Mental retardation, X-linked 91, 300577; cerebral palsy; intellectual disability; autism spectrum disorder; epilepsy
Mendeliome v0.9305 ABHD16A Seb Lunke Phenotypes for gene: ABHD16A were changed from Spastic paraplegia to Spastic paraplegia; Intellectual Disability; Callosome
Mendeliome v0.9304 ZDHHC15 Zornitza Stark Publications for gene: ZDHHC15 were set to
Intellectual disability syndromic and non-syndromic v0.4163 ABHD16A Lucy Spencer gene: ABHD16A was added
gene: ABHD16A was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ABHD16A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABHD16A were set to PMID: 34587489
Phenotypes for gene: ABHD16A were set to Spastic paraplegia
Added comment: 11 individuals from 6 families with a complicated form of hereditary spastic paraplegia who carry bi-allelic deleterious variants in ABHD16A. Affected individuals present with a similar phenotype consisting of global developmental delay/intellectual disability, progressive spasticity affecting the upper and lower limbs, and corpus callosum and white matter anomalies. Immunoblot analysis on extracts from fibroblasts from four affected individuals demonstrated little to no ABHD16A protein levels compared to controls.
In 5 of the families the affected members were homozygous, 3 of these families were consanguineous. 2 families have the same variant- both families are French-Canadian.
4 missense variants, 1 frameshift, 1 nonsense.
From PMID: 34587489
Sources: Literature
Mendeliome v0.9303 ZDHHC15 Krithika Murali changed review comment from: Lewis et al Neurology Genetics 2021

Functional analysis of 4 ZDHHC15 variants - x2 Jin et al, others identified through GeneMatcher

Yeast cells expressing ZDHHC15 p.L13P (Jin et al, maternally inherited), p.K115R (maternally inherited) and p.S330p were indistinguishable from cells harboring the reference ZDHHC15 allele, however those expressing p.H158R (also reported in Jin et al, maternally inherited) disrupted normal protein function.; to: Lewis et al Neurology Genetics 2021

Functional analysis of 4 ZDHHC15 variants - x2 Jin et al Nat Genet 2020 PMID 32989326, others identified through GeneMatcher

Yeast cells expressing ZDHHC15 p.L13P (Jin et al, maternally inherited), p.K115R (maternally inherited) and p.S330p were indistinguishable from cells harboring the reference ZDHHC15 allele, however those expressing p.H158R (also reported in Jin et al, maternally inherited) disrupted normal protein function.
Mendeliome v0.9303 PANX1 Melanie Marty reviewed gene: PANX1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 33495594, 30918116, 32838805; Phenotypes: Oocyte maturation defect 7, MIM#618550; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia v0.292 RFXANK Zornitza Stark Marked gene: RFXANK as ready
Ataxia v0.292 RFXANK Zornitza Stark Gene: rfxank has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9303 ABHD16A Seb Lunke Classified gene: ABHD16A as Green List (high evidence)
Mendeliome v0.9303 ABHD16A Seb Lunke Gene: abhd16a has been classified as Green List (High Evidence).
Mendeliome v0.9302 ZDHHC15 Krithika Murali reviewed gene: ZDHHC15: Rating: RED; Mode of pathogenicity: None; Publications: 34345675; Phenotypes: cerebral palsy, intellectual disability, autism spectrum disorder, epilepsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia v0.292 RFXANK Zornitza Stark Classified gene: RFXANK as Amber List (moderate evidence)
Ataxia v0.292 RFXANK Zornitza Stark Gene: rfxank has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.130 WLS Teresa Zhao gene: WLS was added
gene: WLS was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: WLS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WLS were set to PMID: 34587386
Phenotypes for gene: WLS were set to Syndromic structural birth defects
Review for gene: WLS was set to GREEN
Added comment: - Homozygous mutations in 10 affected persons from 5 unrelated families.
- Patients had multiorgan defects, including microcephal, facial dysmorphism, foot syndactyly, renal agenesis, alopecia, iris coloboma, and heart defects.
- The mutations affected WLS protein stability and Wnt signaling. Knock-in mice showed tissue and cell vulnerability consistent with Wnt-signaling intensity and individual and collective functions of Wnts in embryogenesis.
Sources: Literature
Mendeliome v0.9302 WIPI2 Zornitza Stark Marked gene: WIPI2 as ready
Mendeliome v0.9302 WIPI2 Zornitza Stark Gene: wipi2 has been classified as Green List (High Evidence).
Mendeliome v0.9302 WIPI2 Zornitza Stark Publications for gene: WIPI2 were set to 30968111
Anophthalmia_Microphthalmia_Coloboma v1.8 WLS Teresa Zhao gene: WLS was added
gene: WLS was added to Anophthalmia_Microphthalmia_Coloboma. Sources: Literature
Mode of inheritance for gene: WLS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WLS were set to PMID: 34587386
Phenotypes for gene: WLS were set to Syndromic structural birth defects
Review for gene: WLS was set to GREEN
Added comment: - Homozygous mutations in 10 affected persons from 5 unrelated families.
- Patients had multiorgan defects, including microcephal, facial dysmorphism, foot syndactyly, renal agenesis, alopecia, iris coloboma, and heart defects.
- The mutations affected WLS protein stability and Wnt signaling. Knock-in mice showed tissue and cell vulnerability consistent with Wnt-signaling intensity and individual and collective functions of Wnts in embryogenesis.
Sources: Literature
Mendeliome v0.9301 WIPI2 Zornitza Stark Classified gene: WIPI2 as Green List (high evidence)
Mendeliome v0.9301 WIPI2 Zornitza Stark Gene: wipi2 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.88 WLS Teresa Zhao gene: WLS was added
gene: WLS was added to Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic. Sources: Literature
Mode of inheritance for gene: WLS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WLS were set to PMID: 34587386
Phenotypes for gene: WLS were set to Syndromic structural birth defects
Review for gene: WLS was set to GREEN
Added comment: - Homozygous mutations in 10 affected persons from 5 unrelated families.
- Patients had multiorgan defects, including microcephal, facial dysmorphism, foot syndactyly, renal agenesis, alopecia, iris coloboma, and heart defects.
- The mutations affected WLS protein stability and Wnt signaling. Knock-in mice showed tissue and cell vulnerability consistent with Wnt-signaling intensity and individual and collective functions of Wnts in embryogenesis.
Sources: Literature
Leukodystrophy v0.233 ATP11A Zornitza Stark Marked gene: ATP11A as ready
Leukodystrophy v0.233 ATP11A Zornitza Stark Gene: atp11a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9300 SNIP1 Seb Lunke Publications for gene: SNIP1 were set to 22279524
Leukodystrophy v0.233 ATP11A Zornitza Stark Classified gene: ATP11A as Amber List (moderate evidence)
Leukodystrophy v0.233 ATP11A Zornitza Stark Gene: atp11a has been classified as Amber List (Moderate Evidence).
Hydrocephalus_Ventriculomegaly v0.97 ATP11A Zornitza Stark Marked gene: ATP11A as ready
Hydrocephalus_Ventriculomegaly v0.97 ATP11A Zornitza Stark Gene: atp11a has been classified as Amber List (Moderate Evidence).
Hydrocephalus_Ventriculomegaly v0.97 ATP11A Zornitza Stark Classified gene: ATP11A as Amber List (moderate evidence)
Hydrocephalus_Ventriculomegaly v0.97 ATP11A Zornitza Stark Gene: atp11a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4163 ATP11A Zornitza Stark Marked gene: ATP11A as ready
Intellectual disability syndromic and non-syndromic v0.4163 ATP11A Zornitza Stark Gene: atp11a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4163 ATP11A Zornitza Stark Classified gene: ATP11A as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.4163 ATP11A Zornitza Stark Gene: atp11a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9299 ATP11A Zornitza Stark Marked gene: ATP11A as ready
Mendeliome v0.9299 ATP11A Zornitza Stark Gene: atp11a has been classified as Amber List (Moderate Evidence).
Congenital diaphragmatic hernia v1.3 LONP1 Seb Lunke Marked gene: LONP1 as ready
Congenital diaphragmatic hernia v1.3 LONP1 Seb Lunke Gene: lonp1 has been classified as Red List (Low Evidence).
Congenital diaphragmatic hernia v1.3 LONP1 Seb Lunke gene: LONP1 was added
gene: LONP1 was added to Congenital diaphragmatic hernia. Sources: Literature
Mode of inheritance for gene: LONP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: LONP1 were set to 34547244
Phenotypes for gene: LONP1 were set to Congenital diaphragmatic hernia
Penetrance for gene: LONP1 were set to Incomplete
Review for gene: LONP1 was set to RED
Added comment: LONP1 described as potential new risk factor for CDH. Putative disruptive variants are enriched by approx a factor 10 fold, but remain rare (up to 3% of studied CDH cohort). Segregation studies in 5 families showed incomplete penetrance, at ~50%. A mouse model with lung specific know-out had impaired lung development, but het mice unaffected.
Sources: Literature
Ataxia v0.291 RFXANK Elena Savva gene: RFXANK was added
gene: RFXANK was added to Ataxia - paediatric. Sources: Literature
Mode of inheritance for gene: RFXANK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RFXANK were set to PMID: 33855173; 23314770; 28676232
Phenotypes for gene: RFXANK were set to Progressive Ataxia and Neurologic Regression; MHC class II deficiency, complementation group B MIM#209920
Review for gene: RFXANK was set to AMBER
Added comment: PMID: 33855173 - 1 family (2 affecteds, 3rd not sequenced) with a homozygous c.271+1G>C splice variant, late-onset immunodeficiency and subacute progressive neurodegenerative disease, including cognition, motor, visual and cerebellar features. MRI demonstrated global cerebral and cerebellar atrophy.

PMID: 23314770 - 1/34 MHCII deficient patients with biallelic variants reported with ataxia. Majority of patients (including patient with ataxia) share a founder variant (c.338-25_338del26).

PMID: 28676232 - single 30 month old patient with ataxic gait and dysarthria and a homozygous PTC.

Summary: 3 patients but uncommon feature, variable expressivity
Sources: Literature
Mendeliome v0.9299 ATP11A Zornitza Stark Classified gene: ATP11A as Amber List (moderate evidence)
Mendeliome v0.9299 ATP11A Zornitza Stark Gene: atp11a has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.18 TRIP4 Zornitza Stark Marked gene: TRIP4 as ready
Cerebellar and Pontocerebellar Hypoplasia v1.18 TRIP4 Zornitza Stark Gene: trip4 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.58 WLS Teresa Zhao gene: WLS was added
gene: WLS was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: WLS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WLS were set to PMID: 34587386
Phenotypes for gene: WLS were set to Syndromic structural birth defects
Review for gene: WLS was set to GREEN
Added comment: - Homozygous mutations in 10 affected persons from 5 unrelated families.
- Patients had multiorgan defects, including microcephal, facial dysmorphism, foot syndactyly, renal agenesis, alopecia, iris coloboma, and heart defects.
- The mutations affected WLS protein stability and Wnt signaling. Knock-in mice showed tissue and cell vulnerability consistent with Wnt-signaling intensity and individual and collective functions of Wnts in embryogenesis.
Sources: Literature
Cerebellar and Pontocerebellar Hypoplasia v1.18 TRIP4 Zornitza Stark Classified gene: TRIP4 as Amber List (moderate evidence)
Cerebellar and Pontocerebellar Hypoplasia v1.18 TRIP4 Zornitza Stark Gene: trip4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9298 WIPI2 Dean Phelan reviewed gene: WIPI2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30968111, 34557665; Phenotypes: global developmental delay, intellectual disability, refractory infantile/childhood-onset epilepsy, progressive tetraplegia with joint contractures, dyskinesia, speech and visual impairment, autistic features, ataxic gait; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9298 WLS Zornitza Stark Marked gene: WLS as ready
Mendeliome v0.9298 WLS Zornitza Stark Gene: wls has been classified as Green List (High Evidence).
Mendeliome v0.9298 WLS Zornitza Stark Classified gene: WLS as Green List (high evidence)
Mendeliome v0.9298 WLS Zornitza Stark Gene: wls has been classified as Green List (High Evidence).
Mendeliome v0.9297 ABHD16A Lucy Spencer gene: ABHD16A was added
gene: ABHD16A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ABHD16A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABHD16A were set to PMID: 34587489
Phenotypes for gene: ABHD16A were set to Spastic paraplegia
Review for gene: ABHD16A was set to GREEN
Added comment: 11 individuals from 6 families with a complicated form of hereditary spastic paraplegia who carry bi-allelic deleterious variants in ABHD16A. Affected individuals present with a similar phenotype consisting of global developmental delay/intellectual disability, progressive spasticity affecting the upper and lower limbs, and corpus callosum and white matter anomalies. Immunoblot analysis on extracts from fibroblasts from four affected individuals demonstrated little to no ABHD16A protein levels compared to controls.
In 5 of the families the affected members were homozygous, 3 of these families were consanguineous. 2 families have the same variant- both families are French-Canadian.
4 missense variants, 1 frameshift, 1 nonsense.
From PMID: 34587489
Sources: Literature
Mendeliome v0.9297 SNIP1 Teresa Zhao reviewed gene: SNIP1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 34570759; Phenotypes: Psychomotor retardation, epilepsy, and craniofacial dysmorphism, 614501; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Regression v0.379 SHQ1 Zornitza Stark Marked gene: SHQ1 as ready
Regression v0.379 SHQ1 Zornitza Stark Gene: shq1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4162 ATP11A Elena Savva gene: ATP11A was added
gene: ATP11A was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ATP11A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ATP11A were set to PMID: 34403372
Phenotypes for gene: ATP11A were set to Neurological disorder
Mode of pathogenicity for gene: ATP11A was set to Other
Review for gene: ATP11A was set to AMBER
Added comment: PMID: 34403372:
- Single de novo missense variant reported in a patient with developmental delay and neurological deterioration.
- Patient MRI showed severe cerebral atrophy, ventriculomegaly, hypomyelination leukodystrophy, thinned corpus callosum. Axonal neuropathy suggested.
- K/I heterozygous mice died perinatally.
- Functional studies on missense variant show plasma membrane lipid content impairment, reduced ATPase activity etc.

gnomAD: some NMD PTCs present, good quality variants found with 4-5 hets.
Sources: Literature
Regression v0.379 SHQ1 Zornitza Stark Classified gene: SHQ1 as Amber List (moderate evidence)
Regression v0.379 SHQ1 Zornitza Stark Gene: shq1 has been classified as Amber List (Moderate Evidence).
Regression v0.378 SHQ1 Zornitza Stark gene: SHQ1 was added
gene: SHQ1 was added to Regression. Sources: Literature
Mode of inheritance for gene: SHQ1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SHQ1 were set to 34542157; 29178645
Phenotypes for gene: SHQ1 were set to Dystonia; Neurodegeneration
Review for gene: SHQ1 was set to AMBER
Added comment: Three unrelated families reported. Family 1: isolated dystonia only; Family 2: dystonia, and neurodegeneration; Family 3: neurodegeneration. Rated Amber as phenotypes likely represent a continuum but currently unclear what proportion have neurodegeneration.
Sources: Literature
Hydrocephalus_Ventriculomegaly v0.96 ATP11A Elena Savva gene: ATP11A was added
gene: ATP11A was added to Hydrocephalus_Ventriculomegaly. Sources: Literature
Mode of inheritance for gene: ATP11A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ATP11A were set to PMID: 34403372
Phenotypes for gene: ATP11A were set to Neurological disorder
Mode of pathogenicity for gene: ATP11A was set to Other
Review for gene: ATP11A was set to AMBER
Added comment: PMID: 34403372:
- Single de novo missense variant reported in a patient with developmental delay and neurological deterioration.
- Patient MRI showed severe cerebral atrophy, ventriculomegaly, hypomyelination leukodystrophy, thinned corpus callosum. Axonal neuropathy suggested.
- K/I heterozygous mice died perinatally.
- Functional studies on missense variant show plasma membrane lipid content impairment, reduced ATPase activity etc.

gnomAD: some NMD PTCs present, good quality variants found with 4-5 hets.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4162 ERBB4 Ain Roesley edited their review of gene: ERBB4: Changed phenotypes: intellectual disability
Leukodystrophy v0.232 ATP11A Elena Savva gene: ATP11A was added
gene: ATP11A was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: ATP11A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ATP11A were set to PMID: 34403372
Phenotypes for gene: ATP11A were set to PMID: 34403372
Mode of pathogenicity for gene: ATP11A was set to Other
Review for gene: ATP11A was set to AMBER
Added comment: PMID: 34403372:
- Single de novo missense variant reported in a patient with developmental delay and neurological deterioration.
- Patient MRI showed severe cerebral atrophy, ventriculomegaly, hypomyelination leukodystrophy, thinned corpus callosum. Axonal neuropathy suggested.
- K/I heterozygous mice died perinatally.
- Functional studies on missense variant show plasma membrane lipid content impairment, reduced ATPase activity etc.

gnomAD: some NMD PTCs present, good quality variants found with 4-5 hets.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4162 ERBB4 Ain Roesley gene: ERBB4 was added
gene: ERBB4 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ERBB4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ERBB4 were set to 33603162
Penetrance for gene: ERBB4 were set to unknown
Review for gene: ERBB4 was set to GREEN
Added comment: CNVs reported only
exonic deletions:
3x families with ID, speech delays, aggressive outbursts (including 1x de novo)
1x family with global dev delay inherited from unaffected parent

exonic del with limited clinical info:
1x severe expressive language delay
Sources: Literature
Mendeliome v0.9297 ATP11A Elena Savva gene: ATP11A was added
gene: ATP11A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATP11A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ATP11A were set to PMID: 34403372
Phenotypes for gene: ATP11A were set to Neurological disorder
Mode of pathogenicity for gene: ATP11A was set to Other
Review for gene: ATP11A was set to AMBER
Added comment: PMID: 34403372:
- Single de novo missense variant reported in a patient with developmental delay and neurological deterioration.
- Patient MRI showed severe cerebral atrophy, ventriculomegaly, hypomyelination leukodystrophy, thinned corpus callosum. Axonal neuropathy suggested.
- K/I heterozygous mice died perinatally.
- Functional studies on missense variant show plasma membrane lipid content impairment, reduced ATPase activity etc.

gnomAD: some NMD PTCs present, good quality variants found with 4-5 hets.
Sources: Literature
Cerebellar and Pontocerebellar Hypoplasia v1.17 TRIP4 Chern Lim gene: TRIP4 was added
gene: TRIP4 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Literature
Mode of inheritance for gene: TRIP4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIP4 were set to PMID: 34075209
Phenotypes for gene: TRIP4 were set to cerebellar hypoplasia and spinal muscular atrophy (PCH1) and congenital bone fractures.
Review for gene: TRIP4 was set to AMBER
gene: TRIP4 was marked as current diagnostic
Added comment: PMID: 34075209:
One patient with cerebellar hypoplasia and spinal muscular atrophy (PCH1) and congenital bone fractures, hom PTV. The same PTV had been previously reported in 3 patients from 2 families with prenatal spinal muscular atrophy and congenital bone fractures (PMID: 26924529).
Sources: Literature
Dystonia and Chorea v0.194 SHQ1 Zornitza Stark Marked gene: SHQ1 as ready
Dystonia and Chorea v0.194 SHQ1 Zornitza Stark Gene: shq1 has been classified as Amber List (Moderate Evidence).
Dystonia and Chorea v0.194 SHQ1 Zornitza Stark Classified gene: SHQ1 as Amber List (moderate evidence)
Dystonia and Chorea v0.194 SHQ1 Zornitza Stark Gene: shq1 has been classified as Amber List (Moderate Evidence).
Dystonia and Chorea v0.193 SHQ1 Zornitza Stark gene: SHQ1 was added
gene: SHQ1 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: SHQ1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SHQ1 were set to 34542157; 29178645
Phenotypes for gene: SHQ1 were set to Dystonia; Neurodegeneration
Review for gene: SHQ1 was set to AMBER
Added comment: Three unrelated families reported. Family 1: isolated dystonia only; Family 2: dystonia, and neurodegeneration; Family 3: neurodegeneration. Rated Amber as phenotypes likely represent a continuum but currently unclear what proportion will have complex dystonia.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4162 SARS Bryony Thompson Marked gene: SARS as ready
Intellectual disability syndromic and non-syndromic v0.4162 SARS Bryony Thompson Gene: sars has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4162 SARS Bryony Thompson Classified gene: SARS as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.4162 SARS Bryony Thompson Gene: sars has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9297 WLS Teresa Zhao changed review comment from: - We identified homozygous mutations in 10 affected persons from 5 unrelated families.
- Patients had multiorgan defects, including microcephal, facial dysmorphism, foot syndactyly, renal agenesis, alopecia, iris coloboma, and heart defects.
- The mutations affected WLS protein stability and Wnt signaling. Knock-in mice showed tissue and cell vulnerability consistent with Wnt-signaling intensity and individual and collective functions of Wnts in embryogenesis.
Sources: Literature; to: - Homozygous mutations in 10 affected persons from 5 unrelated families.
- Patients had multiorgan defects, including microcephal, facial dysmorphism, foot syndactyly, renal agenesis, alopecia, iris coloboma, and heart defects.
- The mutations affected WLS protein stability and Wnt signaling. Knock-in mice showed tissue and cell vulnerability consistent with Wnt-signaling intensity and individual and collective functions of Wnts in embryogenesis.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4161 SARS Bryony Thompson gene: SARS was added
gene: SARS was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SARS were set to 28236339; 34570399
Phenotypes for gene: SARS were set to Intellectual disability
Review for gene: SARS was set to AMBER
Added comment: Summary - 2 unrelated families with overlapping ID phenotype, and supporting in vitro and patient cell assays.
PMID: 28236339 - an Iranian family (distantly related) segregating a homozygous missense (c.514G>A, p.Asp172Asn) with moderate ID, microcephaly, ataxia, speech impairment, and aggressive behaviour. Also, supporting in vitro functional assays demonstrating altered protein function.
PMID: 34570399 - a consanguineous Turkish family segregating a homozygous missense (c.638G>T, p.(Arg213Leu)) with developmental delay, central deafness, cardiomyopathy, and metabolic decompensation during fever leading to death. Also, reduced protein level and enzymatic activity in patient cells.
Sources: Literature
Mendeliome v0.9297 WLS Teresa Zhao gene: WLS was added
gene: WLS was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WLS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WLS were set to PMID: 34587386
Phenotypes for gene: WLS were set to Syndromic structural birth defects
Review for gene: WLS was set to GREEN
Added comment: - We identified homozygous mutations in 10 affected persons from 5 unrelated families.
- Patients had multiorgan defects, including microcephal, facial dysmorphism, foot syndactyly, renal agenesis, alopecia, iris coloboma, and heart defects.
- The mutations affected WLS protein stability and Wnt signaling. Knock-in mice showed tissue and cell vulnerability consistent with Wnt-signaling intensity and individual and collective functions of Wnts in embryogenesis.
Sources: Literature
Mendeliome v0.9297 SHQ1 Zornitza Stark Marked gene: SHQ1 as ready
Mendeliome v0.9297 SHQ1 Zornitza Stark Gene: shq1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9297 SARS Bryony Thompson Marked gene: SARS as ready
Mendeliome v0.9297 SARS Bryony Thompson Gene: sars has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9297 SHQ1 Zornitza Stark Classified gene: SHQ1 as Amber List (moderate evidence)
Mendeliome v0.9297 SHQ1 Zornitza Stark Gene: shq1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9296 SHQ1 Zornitza Stark gene: SHQ1 was added
gene: SHQ1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SHQ1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SHQ1 were set to 34542157; 29178645
Phenotypes for gene: SHQ1 were set to Dystonia; Neurodegeneration
Review for gene: SHQ1 was set to AMBER
Added comment: Three unrelated families reported. Family 1: isolated dystonia only; Family 2: dystonia, and neurodegeneration; Family 3: neurodegeneration.

Rated Amber as phenotypes likely represent a continuum but currently unclear.
Sources: Literature
Mendeliome v0.9295 SARS Bryony Thompson Classified gene: SARS as Amber List (moderate evidence)
Mendeliome v0.9295 SARS Bryony Thompson Gene: sars has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9294 SARS Bryony Thompson gene: SARS was added
gene: SARS was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SARS were set to 28236339; 34570399
Phenotypes for gene: SARS were set to Intellectual disability
Review for gene: SARS was set to AMBER
Added comment: Summary - 2 unrelated families with overlapping ID phenotype, and supporting in vitro and patient cell assays.
PMID: 28236339 - an Iranian family (distantly related) segregating a homozygous missense (c.514G>A, p.Asp172Asn) with moderate ID, microcephaly, ataxia, speech impairment, and aggressive behaviour. Also, supporting in vitro functional assays demonstrating altered protein function.
PMID: 34570399 - a consanguineous Turkish family segregating a homozygous missense (c.638G>T, p.(Arg213Leu)) with developmental delay, central deafness, cardiomyopathy, and metabolic decompensation during fever leading to death. Also, reduced protein level and enzymatic activity in patient cells.
Sources: Literature
Macrocephaly_Megalencephaly v0.88 NFIB Zornitza Stark Tag SV/CNV tag was added to gene: NFIB.
Macrocephaly_Megalencephaly v0.88 NFIB Zornitza Stark Marked gene: NFIB as ready
Macrocephaly_Megalencephaly v0.88 NFIB Zornitza Stark Gene: nfib has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.88 NFIB Zornitza Stark Phenotypes for gene: NFIB were changed from to Macrocephaly, acquired, with impaired intellectual development, MIM#618286
Macrocephaly_Megalencephaly v0.87 NFIB Zornitza Stark Publications for gene: NFIB were set to
Macrocephaly_Megalencephaly v0.86 NFIB Zornitza Stark Mode of inheritance for gene: NFIB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Macrocephaly_Megalencephaly v0.85 NFIB Zornitza Stark reviewed gene: NFIB: Rating: GREEN; Mode of pathogenicity: None; Publications: 30388402; Phenotypes: Macrocephaly, acquired, with impaired intellectual development, MIM#618286; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9293 NDN Zornitza Stark Marked gene: NDN as ready
Mendeliome v0.9293 NDN Zornitza Stark Gene: ndn has been classified as Red List (Low Evidence).
Mendeliome v0.9293 NDN Zornitza Stark Phenotypes for gene: NDN were changed from to Prader-Willi syndrome, MIM# 176270
Mendeliome v0.9292 NDN Zornitza Stark Mode of inheritance for gene: NDN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9291 NDN Zornitza Stark Classified gene: NDN as Red List (low evidence)
Mendeliome v0.9291 NDN Zornitza Stark Gene: ndn has been classified as Red List (Low Evidence).
Mendeliome v0.9290 NDN Zornitza Stark reviewed gene: NDN: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Prader-Willi syndrome, MIM# 176270; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4160 NDN Zornitza Stark Phenotypes for gene: NDN were changed from to Prader-Willi syndrome, MIM# 176270
Mendeliome v0.9290 NFIB Zornitza Stark Marked gene: NFIB as ready
Mendeliome v0.9290 NFIB Zornitza Stark Gene: nfib has been classified as Green List (High Evidence).
Mendeliome v0.9290 NFIB Zornitza Stark Phenotypes for gene: NFIB were changed from to Macrocephaly, acquired, with impaired intellectual development, MIM#618286
Mendeliome v0.9289 NFIB Zornitza Stark Publications for gene: NFIB were set to
Mendeliome v0.9288 NFIB Zornitza Stark Mode of inheritance for gene: NFIB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9287 NFIB Zornitza Stark Tag SV/CNV tag was added to gene: NFIB.
Mendeliome v0.9287 NFIB Zornitza Stark reviewed gene: NFIB: Rating: GREEN; Mode of pathogenicity: None; Publications: 30388402; Phenotypes: Macrocephaly, acquired, with impaired intellectual development, MIM#618286; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9287 ZNF407 Zornitza Stark Phenotypes for gene: ZNF407 were changed from Global developmental delay; Intellectual disability to SIMHA syndrome, MIM# 619557; Global developmental delay; Intellectual disability
Mendeliome v0.9286 ZNF407 Zornitza Stark edited their review of gene: ZNF407: Changed phenotypes: SIMHA syndrome, MIM# 619557, Global developmental delay, Intellectual disability
Intellectual disability syndromic and non-syndromic v0.4159 ZNF407 Zornitza Stark Phenotypes for gene: ZNF407 were changed from Global developmental delay; Intellectual disability to SIMHA syndrome, MIM# 619557; Global developmental delay; Intellectual disability
Intellectual disability syndromic and non-syndromic v0.4158 ZNF407 Zornitza Stark edited their review of gene: ZNF407: Changed rating: AMBER; Changed phenotypes: SIMHA syndrome, MIM# 619557; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Growth failure v1.9 RNF113A Zornitza Stark Marked gene: RNF113A as ready
Growth failure v1.9 RNF113A Zornitza Stark Gene: rnf113a has been classified as Green List (High Evidence).
Growth failure v1.9 RNF113A Zornitza Stark Classified gene: RNF113A as Green List (high evidence)
Growth failure v1.9 RNF113A Zornitza Stark Gene: rnf113a has been classified as Green List (High Evidence).
Growth failure v1.8 RNF113A Zornitza Stark gene: RNF113A was added
gene: RNF113A was added to Growth failure. Sources: Expert Review
Mode of inheritance for gene: RNF113A was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: RNF113A were set to 25612912; 31793730; 31880405
Phenotypes for gene: RNF113A were set to Trichothiodystrophy 5, nonphotosensitive; OMIM #300953
Review for gene: RNF113A was set to GREEN
Added comment: Four families reported, two with same variant. Clinical features include ID, microcephaly, IUGR/growth failure, hypogonadism, and sparse/brittle hair. One of the families had antenatal presentation.
Sources: Expert Review
Chromosome Breakage Disorders v1.5 RNF113A Zornitza Stark Marked gene: RNF113A as ready
Chromosome Breakage Disorders v1.5 RNF113A Zornitza Stark Gene: rnf113a has been classified as Green List (High Evidence).
Chromosome Breakage Disorders v1.5 RNF113A Zornitza Stark Classified gene: RNF113A as Green List (high evidence)
Chromosome Breakage Disorders v1.5 RNF113A Zornitza Stark Gene: rnf113a has been classified as Green List (High Evidence).
Chromosome Breakage Disorders v1.4 RNF113A Zornitza Stark gene: RNF113A was added
gene: RNF113A was added to Chromosome Breakage Disorders. Sources: Expert Review
Mode of inheritance for gene: RNF113A was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: RNF113A were set to 25612912; 31793730; 31880405
Phenotypes for gene: RNF113A were set to Trichothiodystrophy 5, nonphotosensitive; OMIM #300953
Review for gene: RNF113A was set to GREEN
Added comment: Four families reported, two with same variant. Clinical features include ID, microcephaly, IUGR/growth failure, hypogonadism, and sparse/brittle hair.
Sources: Expert Review
Microcephaly v1.58 RNF113A Zornitza Stark edited their review of gene: RNF113A: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Microcephaly v1.58 RNF113A Zornitza Stark Publications for gene: RNF113A were set to 25612912; 31793730
Microcephaly v1.57 RNF113A Zornitza Stark Classified gene: RNF113A as Green List (high evidence)
Microcephaly v1.57 RNF113A Zornitza Stark Gene: rnf113a has been classified as Green List (High Evidence).
Microcephaly v1.56 RNF113A Zornitza Stark edited their review of gene: RNF113A: Added comment: Two more individuals reported with different variants, at least one had microcephaly, upgrade to Green.; Changed rating: GREEN; Changed publications: 25612912, 31793730, 31880405
Intellectual disability syndromic and non-syndromic v0.4158 RNF113A Zornitza Stark Publications for gene: RNF113A were set to PMID: 25612912; 31793730
Intellectual disability syndromic and non-syndromic v0.4157 RNF113A Zornitza Stark Classified gene: RNF113A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4157 RNF113A Zornitza Stark Gene: rnf113a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4156 RNF113A Zornitza Stark reviewed gene: RNF113A: Rating: GREEN; Mode of pathogenicity: None; Publications: 31880405; Phenotypes: Trichothiodystrophy 5, nonphotosensitive, OMIM #300953; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.4156 RNF113A Zornitza Stark Mode of inheritance for gene: RNF113A was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Pituitary hormone deficiency v0.20 CHD7 Zornitza Stark Marked gene: CHD7 as ready
Pituitary hormone deficiency v0.20 CHD7 Zornitza Stark Gene: chd7 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.20 CHD7 Zornitza Stark Publications for gene: CHD7 were set to
Pituitary hormone deficiency v0.19 CHD7 Zornitza Stark reviewed gene: CHD7: Rating: GREEN; Mode of pathogenicity: None; Publications: 18834967; Phenotypes: Hypogonadotropic hypogonadism 5 with or without anosmia, MIM# 612370; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v1.56 EIF3F Zornitza Stark Phenotypes for gene: EIF3F were changed from EIF3F-related neurodevelopmental disorder to EIF3F-related neurodevelopmental disorder; Mental retardation, autosomal recessive 67, MIM# 618295
Microcephaly v1.55 EIF3F Zornitza Stark reviewed gene: EIF3F: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, autosomal recessive 67, MIM# 618295; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.55 EIF3F Zornitza Stark Marked gene: EIF3F as ready
Microcephaly v1.55 EIF3F Zornitza Stark Gene: eif3f has been classified as Green List (High Evidence).
Mendeliome v0.9286 EIF3F Zornitza Stark Publications for gene: EIF3F were set to 30409806
Mendeliome v0.9285 EIF3F Zornitza Stark edited their review of gene: EIF3F: Added comment: Hüffmeier et al (2021) reported 21 patients who were homozygous/compound heterozygous for Phe232Val variant in EIF3F. All affected individuals had developmental delay and speech delay. About half had behavioural problems, altered muscular tone, hearing loss, and short stature. The study suggests that microcephaly, reduced sensitivity to pain, cleft lip/palate, gastrointestinal symptoms and ophthalmological symptoms are part of the phenotypic spectrum.; Changed publications: 30409806, 33736665; Changed phenotypes: Mental retardation, autosomal recessive 67, MIM# 618295
Clefting disorders v0.142 EIF3F Zornitza Stark Marked gene: EIF3F as ready
Clefting disorders v0.142 EIF3F Zornitza Stark Gene: eif3f has been classified as Green List (High Evidence).
Clefting disorders v0.142 EIF3F Zornitza Stark Phenotypes for gene: EIF3F were changed from EIF3F-related neurodevelopmental disorder to EIF3F-related neurodevelopmental disorder; Mental retardation, autosomal recessive 67, MIM# 618295
Intellectual disability syndromic and non-syndromic v0.4155 EIF3F Zornitza Stark Publications for gene: EIF3F were set to 30409806
Microcephaly v1.55 EIF3F Chirag Patel Classified gene: EIF3F as Green List (high evidence)
Microcephaly v1.55 EIF3F Chirag Patel Gene: eif3f has been classified as Green List (High Evidence).
Microcephaly v1.54 EIF3F Chirag Patel gene: EIF3F was added
gene: EIF3F was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: EIF3F was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EIF3F were set to PMID: 33736665
Phenotypes for gene: EIF3F were set to EIF3F-related neurodevelopmental disorder
Review for gene: EIF3F was set to GREEN
Added comment: Hüffmeier et al (2021) reported 21 patients who were homozygous/compound heterozygous for Phe232Val variant in EIF3F. All affected individuals had developmental delay and speech delay. About half had behavioural problems, altered muscular tone, hearing loss, and short stature. The study suggests that microcephaly, reduced sensitivity to pain, cleft lip/palate, gastrointestinal symptoms and ophthalmological symptoms are part of the phenotypic spectrum.
Sources: Literature
Clefting disorders v0.141 EIF3F Chirag Patel Classified gene: EIF3F as Green List (high evidence)
Clefting disorders v0.141 EIF3F Chirag Patel Gene: eif3f has been classified as Green List (High Evidence).
Clefting disorders v0.140 EIF3F Chirag Patel gene: EIF3F was added
gene: EIF3F was added to Clefting disorders. Sources: Literature
Mode of inheritance for gene: EIF3F was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EIF3F were set to PMID: 33736665
Phenotypes for gene: EIF3F were set to EIF3F-related neurodevelopmental disorder
Review for gene: EIF3F was set to GREEN
Added comment: Hüffmeier et al (2021) reported 21 patients who were homozygous/compound heterozygous for Phe232Val variant in EIF3F. All affected individuals had developmental delay and speech delay. About half had behavioural problems, altered muscular tone, hearing loss, and short stature. The study suggests that microcephaly, reduced sensitivity to pain, cleft lip/palate, gastrointestinal symptoms and ophthalmological symptoms are part of the phenotypic spectrum.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4154 EIF3F Chirag Patel reviewed gene: EIF3F: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33736665; Phenotypes: EIF3F-related neurodevelopmental disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Growth failure v1.7 KMT2A Zornitza Stark Marked gene: KMT2A as ready
Growth failure v1.7 KMT2A Zornitza Stark Added comment: Comment when marking as ready: Short stature is a feature.
Growth failure v1.7 KMT2A Zornitza Stark Gene: kmt2a has been classified as Green List (High Evidence).
Growth failure v1.7 KMT2A Zornitza Stark Publications for gene: KMT2A were set to PubMed: 22795537, 25810209, 29574747, 33783954
Growth failure v1.6 KMT2A Chirag Patel Classified gene: KMT2A as Green List (high evidence)
Growth failure v1.6 KMT2A Chirag Patel Gene: kmt2a has been classified as Green List (High Evidence).
Growth failure v1.5 KMT2A Chirag Patel gene: KMT2A was added
gene: KMT2A was added to Growth failure. Sources: Literature
Mode of inheritance for gene: KMT2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KMT2A were set to PubMed: 22795537, 25810209, 29574747, 33783954
Phenotypes for gene: KMT2A were set to Wiedemann-Steiner syndrome; OMIM #605130
Review for gene: KMT2A was set to GREEN
Added comment: Wiedemann-Steiner syndrome is a congenital malformation syndrome characteriSed by hypertrichosis cubiti/back, short stature/growth retardation, mild to moderate intellectual disability; behavioral difficulties, and dysmorphism (long eyelashes, thick/arched eyebrows with lateral flare, broad nasal bridge, and downslanting and vertically narrow palpebral fissures). Many patients reported in the literature.
Sources: Literature
Cerebral Palsy v0.186 MFN2 Zornitza Stark Marked gene: MFN2 as ready
Cerebral Palsy v0.186 MFN2 Zornitza Stark Gene: mfn2 has been classified as Red List (Low Evidence).
Cerebral Palsy v0.186 MFN2 Zornitza Stark Classified gene: MFN2 as Red List (low evidence)
Cerebral Palsy v0.186 MFN2 Zornitza Stark Gene: mfn2 has been classified as Red List (Low Evidence).
Cerebral Palsy v0.185 SAMHD1 Zornitza Stark Marked gene: SAMHD1 as ready
Cerebral Palsy v0.185 SAMHD1 Zornitza Stark Gene: samhd1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.185 RNASEH2C Zornitza Stark Marked gene: RNASEH2C as ready
Cerebral Palsy v0.185 RNASEH2C Zornitza Stark Gene: rnaseh2c has been classified as Green List (High Evidence).
Cerebral Palsy v0.185 RNASEH2A Zornitza Stark Marked gene: RNASEH2A as ready
Cerebral Palsy v0.185 RNASEH2A Zornitza Stark Gene: rnaseh2a has been classified as Green List (High Evidence).
Cerebral Palsy v0.185 RNASEH2B Zornitza Stark Marked gene: RNASEH2B as ready
Cerebral Palsy v0.185 RNASEH2B Zornitza Stark Gene: rnaseh2b has been classified as Green List (High Evidence).
Cerebral Palsy v0.185 RNASEH2B Zornitza Stark Publications for gene: RNASEH2B were set to PMID: 17846997, 28762473
Cerebral Palsy v0.184 TREX1 Zornitza Stark Marked gene: TREX1 as ready
Cerebral Palsy v0.184 TREX1 Zornitza Stark Gene: trex1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.184 TREX1 Zornitza Stark Publications for gene: TREX1 were set to PMID: 17846997, 33528536
Cerebral Palsy v0.183 TAF1 Zornitza Stark Marked gene: TAF1 as ready
Cerebral Palsy v0.183 TAF1 Zornitza Stark Gene: taf1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.183 TAF1 Zornitza Stark Publications for gene: TAF1 were set to PMID: 26637982, 33528536, 17273961
Cerebral Palsy v0.182 SPTAN1 Zornitza Stark Marked gene: SPTAN1 as ready
Cerebral Palsy v0.182 SPTAN1 Zornitza Stark Gene: sptan1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.182 SPTAN1 Zornitza Stark Publications for gene: SPTAN1 were set to PMID: 20493457, 33528536, 34364746
Cerebral Palsy v0.181 ZSWIM6 Zornitza Stark Marked gene: ZSWIM6 as ready
Cerebral Palsy v0.181 ZSWIM6 Zornitza Stark Gene: zswim6 has been classified as Green List (High Evidence).
Cerebral Palsy v0.181 SAMHD1 Chirag Patel Classified gene: SAMHD1 as Green List (high evidence)
Cerebral Palsy v0.181 SAMHD1 Chirag Patel Gene: samhd1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.180 SAMHD1 Chirag Patel gene: SAMHD1 was added
gene: SAMHD1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SAMHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SAMHD1 were set to PMID: 19525956
Phenotypes for gene: SAMHD1 were set to Aicardi-Goutieres syndrome 5; OMIM #612952
Review for gene: SAMHD1 was set to GREEN
Added comment: Aicardi-Goutieres syndrome is characterised by cerebral atrophy, leukodystrophy, intracranial calcifications, chronic CSF lymphocytosis, and increased CSF alpha-interferon, and neurologic dysfunction (progressive microcephaly, spasticity, dystonic posturing, profound psychomotor retardation), and often death in early childhood.

Rice et al. (2009) reported biallelic SAMHD1 mutations in 13 families with AGS.
Sources: Literature
Cerebral Palsy v0.179 RNASEH2C Chirag Patel Classified gene: RNASEH2C as Green List (high evidence)
Cerebral Palsy v0.179 RNASEH2C Chirag Patel Gene: rnaseh2c has been classified as Green List (High Evidence).
Cerebral Palsy v0.178 RNASEH2C Chirag Patel gene: RNASEH2C was added
gene: RNASEH2C was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: RNASEH2C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASEH2C were set to PMID: 17846997
Phenotypes for gene: RNASEH2C were set to Aicardi-Goutieres syndrome 3; OMIM #610329
Review for gene: RNASEH2C was set to GREEN
Added comment: Aicardi-Goutieres syndrome is characterised by cerebral atrophy, leukodystrophy, intracranial calcifications, chronic CSF lymphocytosis, and increased CSF alpha-interferon, and neurologic dysfunction (progressive microcephaly, spasticity, dystonic posturing, profound psychomotor retardation), and often death in early childhood.

Rice et al. (2007) reported biallelic RNASEH2C mutations in 18 families with AGS.
Sources: Literature
Cerebral Palsy v0.177 RNASEH2A Chirag Patel Classified gene: RNASEH2A as Green List (high evidence)
Cerebral Palsy v0.177 RNASEH2A Chirag Patel Gene: rnaseh2a has been classified as Green List (High Evidence).
Cerebral Palsy v0.176 RNASEH2B Chirag Patel Classified gene: RNASEH2B as Green List (high evidence)
Cerebral Palsy v0.176 RNASEH2B Chirag Patel Gene: rnaseh2b has been classified as Green List (High Evidence).
Cerebral Palsy v0.176 RNASEH2A Chirag Patel gene: RNASEH2A was added
gene: RNASEH2A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: RNASEH2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASEH2A were set to PMID: 17846997
Phenotypes for gene: RNASEH2A were set to Aicardi-Goutieres syndrome 4; OMIM #610333
Review for gene: RNASEH2A was set to GREEN
Added comment: Aicardi-Goutieres syndrome is characterised by cerebral atrophy, leukodystrophy, intracranial calcifications, chronic CSF lymphocytosis, and increased CSF alpha-interferon, and neurologic dysfunction (progressive microcephaly, spasticity, dystonic posturing, profound psychomotor retardation), and often death in early childhood.

Rice et al. (2007) reported biallelic RNASEH2A mutations in 3 families with AGS.
Sources: Literature
Cerebral Palsy v0.175 RNASEH2B Chirag Patel gene: RNASEH2B was added
gene: RNASEH2B was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: RNASEH2B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASEH2B were set to PMID: 17846997, 28762473
Phenotypes for gene: RNASEH2B were set to Aicardi-Goutieres syndrome 2; OMIM #610181
Review for gene: RNASEH2B was set to GREEN
Added comment: Aicardi-Goutieres syndrome is characterised by cerebral atrophy, leukodystrophy, intracranial calcifications, chronic CSF lymphocytosis, and increased CSF alpha-interferon, and neurologic dysfunction (progressive microcephaly, spasticity, dystonic posturing, profound psychomotor retardation), and often death in early childhood.

Rice et al. (2007) reported biallelic RNASEH2B mutations in 47 families with AGS.

Svingen et al. (2017) reported 2 siblings with atypical AGS with spastic quadriplegia, anarthria, preserved intellect, and increased iron signal in basal ganglia and homozygous RNASEH2B pathogenic variant.
Sources: Literature
Cerebral Palsy v0.174 TREX1 Chirag Patel Classified gene: TREX1 as Green List (high evidence)
Cerebral Palsy v0.174 TREX1 Chirag Patel Gene: trex1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.173 TREX1 Chirag Patel gene: TREX1 was added
gene: TREX1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TREX1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TREX1 were set to PMID: 17846997, 33528536
Phenotypes for gene: TREX1 were set to Aicardi-Goutieres syndrome 1, dominant and recessive, OMIM #225750
Review for gene: TREX1 was set to GREEN
Added comment: Aicardi-Goutieres syndrome is characterised by cerebral atrophy, leukodystrophy, intracranial calcifications, chronic CSF lymphocytosis, and increased CSF alpha-interferon, and neurologic dysfunction (progressive microcephaly, spasticity, dystonic posturing, profound psychomotor retardation), and often death in early childhood.

Rice et al. (2007) reported biallelic TREX1 mutations in 31 families with AGS, and de novo heterozygous TREX1 mutation in 1 patient with AGS.

Moreno-De-Luca et al. (2021) reported 1 patient with CP and paternally inherited pathogenic variant.
Sources: Literature
Cerebral Palsy v0.172 TAF1 Chirag Patel Classified gene: TAF1 as Green List (high evidence)
Cerebral Palsy v0.172 TAF1 Chirag Patel Gene: taf1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.171 TAF1 Chirag Patel gene: TAF1 was added
gene: TAF1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TAF1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: TAF1 were set to PMID: 26637982, 33528536, 17273961
Phenotypes for gene: TAF1 were set to Intellectual developmental disorder, X-linked syndromic 33, OMIM #300966; Dystonia-Parkinsonism, X-linked, OMIM #314250
Review for gene: TAF1 was set to GREEN
Added comment: O'Rawe et al. (2015) reported 12 boys from 9 unrelated families with X-linked global developmental delay, intellectual disability, dysmorphism, generalized hypotonia, microcephaly and variable neurologic features (hypoplastic CC, spastic diplegia, dystonic movements, tremors). They identified 9 different hemizygous mutations in TAF1 gene (most de novo, 3 maternally inherited). No functional studies. The mutations were found by WGS, WES, targeted panel and microarray, and all confirmed by Sanger sequencing.

Moreno-De-Luca et al. (2021) reported 2 patients with CP and de novo LP variant.

Note: X-linked dystonia-parkinsonism (XDP) is caused by an SVA (short interspersed nuclear element, variable number of tandem repeats, and Alu composite) retrotransposon insertion in intron 32 of TAF1, which encodes the largest component of the TFIID complex, and resulted in significantly decreased expression levels of TAF1 and the dopamine receptor D2 gene (DRD2) in the caudate nucleus.
Sources: Literature
Cerebral Palsy v0.170 SPTAN1 Chirag Patel Classified gene: SPTAN1 as Green List (high evidence)
Cerebral Palsy v0.170 SPTAN1 Chirag Patel Gene: sptan1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.169 SPTAN1 Chirag Patel Classified gene: SPTAN1 as Green List (high evidence)
Cerebral Palsy v0.169 SPTAN1 Chirag Patel Gene: sptan1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.168 SPTAN1 Chirag Patel gene: SPTAN1 was added
gene: SPTAN1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SPTAN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPTAN1 were set to PMID: 20493457, 33528536, 34364746
Phenotypes for gene: SPTAN1 were set to Developmental and epileptic encephalopathy 5; OMIM #613477
Review for gene: SPTAN1 was set to GREEN
Added comment: Developmental and epileptic encephalopathy-5 (DEE5) is a neurologic disorder characterised by tonic seizures/infantile spasms in first months of life, global developmental delay, lack of visual attention, poor head control, feeding difficulties, microcephaly, and spastic quadriplegia. Brain imaging may show cerebral atrophy and hypomyelination.

Saitsu et al (2010) reported 2 patients with de novo in-frame mutations of SPTAN1 with early-onset WS with spastic quadriplegia, poor visual attention, and severe developmental delay.
Moreno-De-Luca et al (2021) reported 3 patients with CP with de novo LP/P variants.
Zahrani et al (2021) reported 1 patient with NDD (CP features) with de novo LP variant
Sources: Literature
Cerebral Palsy v0.167 ZSWIM6 Chirag Patel Classified gene: ZSWIM6 as Green List (high evidence)
Cerebral Palsy v0.167 ZSWIM6 Chirag Patel Gene: zswim6 has been classified as Green List (High Evidence).
Cerebral Palsy v0.167 ZSWIM6 Chirag Patel Classified gene: ZSWIM6 as Green List (high evidence)
Cerebral Palsy v0.167 ZSWIM6 Chirag Patel Gene: zswim6 has been classified as Green List (High Evidence).
Cerebral Palsy v0.166 ZSWIM6 Chirag Patel gene: ZSWIM6 was added
gene: ZSWIM6 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ZSWIM6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZSWIM6 were set to PMID: 29198722
Phenotypes for gene: ZSWIM6 were set to Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features, OMIM #617865
Review for gene: ZSWIM6 was set to GREEN
Added comment: Palmer et al. (2017) reported 7 unrelated patients with neurodevelopmental disorder with movement abnormalities spasticity, abnormal gait, and autistic features. WES/WGS identified the same heterozygous R913X variant in exon 13 of ZSWIM6 gene (de novo in 6, unk in 1). The mutation was not found in gnomAD. Analysis of patient cells indicated that the mutant transcript escaped nonsense-mediated mRNA decay, and most likely produced a truncated protein, although antibody studies were unable to detect a truncated protein.

Note: de novo missense variant within C-terminal Sin3-like domain of ZSWIM6 reported to cause acromelic frontonasal dysostosis (AFND), via a proposed gain-of-function effect.
Sources: Literature
Genetic Epilepsy v0.1249 TMTC3 Zornitza Stark Marked gene: TMTC3 as ready
Genetic Epilepsy v0.1249 TMTC3 Zornitza Stark Gene: tmtc3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1249 TMTC3 Zornitza Stark Phenotypes for gene: TMTC3 were changed from Lissencephaly 8 MIM#617255 to Lissencephaly 8, MIM#617255
Genetic Epilepsy v0.1248 TMTC3 Zornitza Stark Classified gene: TMTC3 as Green List (high evidence)
Genetic Epilepsy v0.1248 TMTC3 Zornitza Stark Gene: tmtc3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1247 WDR26 Zornitza Stark Marked gene: WDR26 as ready
Genetic Epilepsy v0.1247 WDR26 Zornitza Stark Gene: wdr26 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1247 WDR26 Zornitza Stark Classified gene: WDR26 as Green List (high evidence)
Genetic Epilepsy v0.1247 WDR26 Zornitza Stark Gene: wdr26 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1246 ZMYND11 Zornitza Stark Marked gene: ZMYND11 as ready
Genetic Epilepsy v0.1246 ZMYND11 Zornitza Stark Gene: zmynd11 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1246 ZMYND11 Zornitza Stark Classified gene: ZMYND11 as Green List (high evidence)
Genetic Epilepsy v0.1246 ZMYND11 Zornitza Stark Gene: zmynd11 has been classified as Green List (High Evidence).
Severe Combined Immunodeficiency v1.0 Zornitza Stark promoted panel to version 1.0
Mendeliome v0.9285 PTPRC Zornitza Stark Marked gene: PTPRC as ready
Mendeliome v0.9285 PTPRC Zornitza Stark Gene: ptprc has been classified as Green List (High Evidence).
Mendeliome v0.9285 PTPRC Zornitza Stark Phenotypes for gene: PTPRC were changed from to Severe combined immunodeficiency, T cell-negative, B-cell/natural killer-cell positive MIM# 608971; Hepatitis C virus, susceptibility to MIM# 609532
Mendeliome v0.9284 PTPRC Zornitza Stark Publications for gene: PTPRC were set to
Mendeliome v0.9283 PTPRC Zornitza Stark Mode of inheritance for gene: PTPRC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9282 PTPRC Zornitza Stark reviewed gene: PTPRC: Rating: GREEN; Mode of pathogenicity: None; Publications: 11145714, 12073144, 22689986, 10700239; Phenotypes: Severe combined immunodeficiency, T cell-negative, B-cell/natural killer-cell positive MIM# 608971, Hepatitis C virus, susceptibility to MIM# 609532; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe Combined Immunodeficiency v0.46 PTPRC Zornitza Stark Marked gene: PTPRC as ready
Severe Combined Immunodeficiency v0.46 PTPRC Zornitza Stark Gene: ptprc has been classified as Green List (High Evidence).
Severe Combined Immunodeficiency v0.46 PTPRC Zornitza Stark Phenotypes for gene: PTPRC were changed from to Severe combined immunodeficiency, T cell-negative, B-cell/natural killer-cell positive MIM# 608971; Hepatitis C virus, susceptibility to MIM# 609532
Severe Combined Immunodeficiency v0.45 PTPRC Zornitza Stark Publications for gene: PTPRC were set to
Severe Combined Immunodeficiency v0.44 PTPRC Zornitza Stark Mode of inheritance for gene: PTPRC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Severe Combined Immunodeficiency v0.43 JAK3 Zornitza Stark Marked gene: JAK3 as ready
Severe Combined Immunodeficiency v0.43 JAK3 Zornitza Stark Gene: jak3 has been classified as Green List (High Evidence).
Severe Combined Immunodeficiency v0.43 JAK3 Zornitza Stark Phenotypes for gene: JAK3 were changed from to SCID, autosomal recessive, T-negative/B-positive type MIM# 600802
Severe Combined Immunodeficiency v0.42 JAK3 Zornitza Stark Publications for gene: JAK3 were set to
Severe Combined Immunodeficiency v0.41 JAK3 Zornitza Stark Mode of inheritance for gene: JAK3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Severe Combined Immunodeficiency v0.40 IL7R Zornitza Stark Marked gene: IL7R as ready
Severe Combined Immunodeficiency v0.40 IL7R Zornitza Stark Gene: il7r has been classified as Green List (High Evidence).
Severe Combined Immunodeficiency v0.40 IL7R Zornitza Stark Phenotypes for gene: IL7R were changed from to Severe combined immunodeficiency, T-cell negative, B-cell/natural killer cell-positive type MIM# 608971; low T-cell numbers; normal-high B and NK-cell numbers; fever; rash; failure to thrive; recurrent respiratory and gastric infections; Hepatomegaly; Splenomegaly; diarrhoea; lymphadenopathy; pneumonitis; Pancytopaenia; decreased immunoglobulins
Severe Combined Immunodeficiency v0.39 IL7R Zornitza Stark Publications for gene: IL7R were set to
Severe Combined Immunodeficiency v0.38 IL7R Zornitza Stark Mode of inheritance for gene: IL7R was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9282 CORO1A Zornitza Stark Marked gene: CORO1A as ready
Mendeliome v0.9282 CORO1A Zornitza Stark Gene: coro1a has been classified as Green List (High Evidence).
Mendeliome v0.9282 CORO1A Zornitza Stark Phenotypes for gene: CORO1A were changed from to Immunodeficiency 8, MIM# 615401
Mendeliome v0.9281 CORO1A Zornitza Stark Publications for gene: CORO1A were set to
Mendeliome v0.9280 CORO1A Zornitza Stark Mode of inheritance for gene: CORO1A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Severe Combined Immunodeficiency v0.37 CORO1A Zornitza Stark Marked gene: CORO1A as ready
Severe Combined Immunodeficiency v0.37 CORO1A Zornitza Stark Gene: coro1a has been classified as Green List (High Evidence).
Severe Combined Immunodeficiency v0.37 CORO1A Zornitza Stark Phenotypes for gene: CORO1A were changed from to Immunodeficiency 8, MIM# 615401
Severe Combined Immunodeficiency v0.36 CORO1A Zornitza Stark Publications for gene: CORO1A were set to
Severe Combined Immunodeficiency v0.35 CORO1A Zornitza Stark Mode of inheritance for gene: CORO1A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9279 POU6F2 Zornitza Stark Marked gene: POU6F2 as ready
Mendeliome v0.9279 POU6F2 Zornitza Stark Added comment: Comment when marking as ready: No evidence for association with Mendelian disease.
Mendeliome v0.9279 POU6F2 Zornitza Stark Gene: pou6f2 has been classified as Red List (Low Evidence).
Mendeliome v0.9279 POU6F2 Zornitza Stark Classified gene: POU6F2 as Red List (low evidence)
Mendeliome v0.9279 POU6F2 Zornitza Stark Gene: pou6f2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1245 TMTC3 Danielle Ariti gene: TMTC3 was added
gene: TMTC3 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: TMTC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMTC3 were set to 27773428; 28973161; 32973946
Phenotypes for gene: TMTC3 were set to Lissencephaly 8 MIM#617255
Review for gene: TMTC3 was set to GREEN
Added comment: 14 individuals from 8 unrelated families reported with bi-allelic LoF (frameshift, deletion, insertion) and missense variants.

Lissencephaly-8 is a neurologic disorder characterised by delayed psychomotor development, ID with poor/absent speech, early-onset refractory seizures, hypotonia and appendicular spasticity.

Seizures are considered a prominent phenotype: 6/9 patients developed refractory generalised or myoclonic seizures in infancy (PMID: 27773428) and in a reported family all four affected siblings presented with nocturnal seizures and ID (PMID: 28973161).
Sources: Expert list
Genetic Epilepsy v0.1245 WDR26 Danielle Ariti gene: WDR26 was added
gene: WDR26 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: WDR26 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WDR26 were set to 28686853; 33675273
Phenotypes for gene: WDR26 were set to Skraban-Deardorff syndrome MIM# 617616
Review for gene: WDR26 was set to GREEN
Added comment: 20 individuals have been reported (only 17 with a clinical description available).

All mono-allelic variants reported were de novo; most variants were LoF (frameshift, nonsense, splice site, deletion) but some were missense.

Skraban-Deardorff syndrome is a neurodevelopmental disorder characterised by a broad range of clinical signs, including ID/DD, febrile and/or non-febrile seizures, abnormal facial features, feeding difficulties, and minor skeletal anomalies (Spastic gait).

PMID: 28686853- Reported 15 individuals with pathogenic de novo WDR26 variants. 15/15 patients presented with both ID and seizures.
Sources: Expert list
Genetic Epilepsy v0.1245 ZMYND11 Danielle Ariti gene: ZMYND11 was added
gene: ZMYND11 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: ZMYND11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZMYND11 were set to 32097528; 34216016
Phenotypes for gene: ZMYND11 were set to Mental retardation, autosomal dominant 30 MIM# 616083
Review for gene: ZMYND11 was set to GREEN
Added comment: ZMYND11 variants are associated with a neurodevelopmental disorder, MRD30 that is characterised by developmental delay, particularly affecting speech, mild‐moderate intellectual disability, significant behavioural abnormalities, seizures, and hypotonia.
* Most identified variants are likely to result in premature truncation and/or nonsense‐mediated decay.

PMID: 34216016- Study of individuals with pathogenic ZMYND11 variants, 20/47 individuals presented with epilepsy (idiopathic focal epilepsy, Rolandic epilepsy, generalised epilepsies, Atypical Benign Partial Epilepsy etc).

PMID: 32097528- Study of 16 patients with ZMYND11-related syndromic intellectual disability, 31% presented with epilepsy.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.4154 CDH15 Zornitza Stark reviewed gene: CDH15: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.9278 CDH15 Zornitza Stark Marked gene: CDH15 as ready
Mendeliome v0.9278 CDH15 Zornitza Stark Gene: cdh15 has been classified as Red List (Low Evidence).
Mendeliome v0.9278 CDH15 Zornitza Stark Phenotypes for gene: CDH15 were changed from to Mental retardation, autosomal dominant 3, MIM#612580
Mendeliome v0.9277 CDH15 Zornitza Stark Publications for gene: CDH15 were set to
Mendeliome v0.9276 CDH15 Zornitza Stark Mode of inheritance for gene: CDH15 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9275 CDH15 Zornitza Stark Classified gene: CDH15 as Red List (low evidence)
Mendeliome v0.9275 CDH15 Zornitza Stark Gene: cdh15 has been classified as Red List (Low Evidence).
Mendeliome v0.9274 CDH15 Zornitza Stark Tag disputed tag was added to gene: CDH15.
Mendeliome v0.9274 CDH15 Zornitza Stark commented on gene: CDH15: PMID: 19012874 - 4 unrelated patients with missense variants and mild-severe ID. Only two genes checked. All variants are common in gnomAD (>20 hets each) and classified as VUS or likely benign in ClinVar (paper is from 2008, pre-dates gnomAD). Functional studies were performed showing a LOF effect, where cell adhesion was reduced.
However NMD PTCs are present in gnomAD (many >=6 hets each)

PMID: 12052883 - null mouse model were viable, showed no gross developmental defects. In particular, the skeletal musculature appeared essentially normal. In the cerebellum of M-cadherin-lacking mutants, typical contactus adherens junctions were present and similar in size and numbers to the equivalent junctions in wild-type animals. However, the adhesion plaques in the cerebellum of these mutants appeared to contain elevated levels of N-cadherin compared to wild-type animals.

PMID: 28422132 - reviewed microdeletions spanning multiple genes including CDH15, suggests it may contribute to a more severe neurological phenotype, with particular regard to brain malformations.

PMID: 26506440 - speculates low penetrance for PTCs in this gene. Acknowledges variants in ExAC, describes them as benign

Note no P/LP variants in ClinVar
Mendeliome v0.9274 CDH15 Zornitza Stark reviewed gene: CDH15: Rating: RED; Mode of pathogenicity: None; Publications: 19012874, 12052883, 28422132, 26506440; Phenotypes: Mental retardation, autosomal dominant 3, MIM#612580; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4154 CDH15 Zornitza Stark Marked gene: CDH15 as ready
Intellectual disability syndromic and non-syndromic v0.4154 CDH15 Zornitza Stark Gene: cdh15 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.4154 CDH15 Zornitza Stark Phenotypes for gene: CDH15 were changed from to Mental retardation, autosomal dominant 3 MIM#612580
Intellectual disability syndromic and non-syndromic v0.4153 CDH15 Zornitza Stark Publications for gene: CDH15 were set to
Severe Combined Immunodeficiency v0.34 PTPRC Danielle Ariti reviewed gene: PTPRC: Rating: GREEN; Mode of pathogenicity: None; Publications: 11145714, 12073144, 22689986, 10700239; Phenotypes: Severe combined immunodeficiency, T cell-negative, B-cell/natural killer-cell positive MIM# 608971, Hepatitis C virus, susceptibility to MIM# 609532; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9274 JAK3 Danielle Ariti reviewed gene: JAK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 14615376, 11668610; Phenotypes: SCID, autosomal recessive, T-negative/B-positive type MIM# 600802; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe Combined Immunodeficiency v0.34 JAK3 Danielle Ariti reviewed gene: JAK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 14615376, 11668610; Phenotypes: SCID, autosomal recessive, T-negative/B-positive type MIM# 600802; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9274 CORO1A Danielle Ariti reviewed gene: CORO1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 25073507, 2352248, 18836449; Phenotypes: Immunodeficiency 8 MIM# 615401; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe Combined Immunodeficiency v0.34 CORO1A Danielle Ariti reviewed gene: CORO1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 25073507, 2352248, 18836449; Phenotypes: Immunodeficiency 8 MIM# 615401; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9274 POU6F2 Chloe Stutterd reviewed gene: POU6F2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Vascular Malformations SuperPanel v1.1 Bryony Thompson Panel status changed from internal to public
Intellectual disability syndromic and non-syndromic v0.4152 CDH15 Zornitza Stark Mode of inheritance for gene: CDH15 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4151 CDH15 Zornitza Stark Tag disputed tag was added to gene: CDH15.
Intellectual disability syndromic and non-syndromic v0.4151 CDH15 Zornitza Stark Classified gene: CDH15 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.4151 CDH15 Zornitza Stark Gene: cdh15 has been classified as Red List (Low Evidence).
Skeletal dysplasia v0.125 FGF8 Zornitza Stark Marked gene: FGF8 as ready
Skeletal dysplasia v0.125 FGF8 Zornitza Stark Gene: fgf8 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.125 FGF8 Zornitza Stark Publications for gene: FGF8 were set to 24569166
Skeletal dysplasia v0.124 FGF8 Zornitza Stark Classified gene: FGF8 as Amber List (moderate evidence)
Skeletal dysplasia v0.124 FGF8 Zornitza Stark Gene: fgf8 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.123 FGF8 Zornitza Stark Tag SV/CNV tag was added to gene: FGF8.
Skeletal dysplasia v0.123 FGF8 Zornitza Stark reviewed gene: FGF8: Rating: AMBER; Mode of pathogenicity: None; Publications: 34433009; Phenotypes: Hypoplastic femurs and pelvis, MIM#619545; Mode of inheritance: None
Mendeliome v0.9274 FGF8 Zornitza Stark Phenotypes for gene: FGF8 were changed from Hypogonadotropic hypogonadism 6 with or without anosmia, MIM# 612702; Femoral hypoplasia to Hypogonadotropic hypogonadism 6 with or without anosmia, MIM# 612702; Hypoplastic femurs and pelvis, MIM#619545
Mendeliome v0.9273 FGF8 Zornitza Stark edited their review of gene: FGF8: Changed phenotypes: Hypogonadotropic hypogonadism 6 with or without anosmia, MIM# 612702, Hypoplastic femurs and pelvis, MIM#619545
Intellectual disability syndromic and non-syndromic v0.4150 CDH15 Elena Savva reviewed gene: CDH15: Rating: RED; Mode of pathogenicity: Other; Publications: PMID: 19012874, 12052883, 28422132, 26506440; Phenotypes: Mental retardation, autosomal dominant 3 MIM#612580; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Vascular Malformations SuperPanel v1.0 Bryony Thompson Added Panel Vasculopathy SuperPanel
Set child panels to: Vascular Malformations_Somatic; Vascular Malformations_Germline; Lymphoedema_nonsyndromic; Lymphoedema_syndromic
Set panel types to: Royal Melbourne Hospital
Mendeliome v0.9273 ARL6IP6 Zornitza Stark Marked gene: ARL6IP6 as ready
Mendeliome v0.9273 ARL6IP6 Zornitza Stark Gene: arl6ip6 has been classified as Red List (Low Evidence).
Mendeliome v0.9273 ARL6IP6 Zornitza Stark gene: ARL6IP6 was added
gene: ARL6IP6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARL6IP6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARL6IP6 were set to 31142202
Phenotypes for gene: ARL6IP6 were set to Cutis marmorata telangiectatica congenita
Review for gene: ARL6IP6 was set to RED
Added comment: A single case reported from a consanguineous family with a homozygous nonsense variant (p.Trp64Ter).
Sources: Literature
Repeat Disorders v0.148 FRA7A Bryony Thompson edited their review of STR: FRA7A: Added comment: Bioinformatic analysis of 544 whole genomes from non-affected individuals demonstrated a range of 5-53 repeats, with a median of 13.; Changed publications: 25196122, 33510257
Repeat Disorders v0.148 FRA2A Bryony Thompson edited their review of STR: FRA2A: Added comment: Bioinformatic analysis of 544 whole genomes from non-affected individuals demonstrated a range of 1-64 repeats, with a median of 16.; Changed publications: 24763282, 33510257
Repeat Disorders v0.148 FRA12A Bryony Thompson edited their review of STR: FRA12A: Added comment: Bioinformatic analysis of 544 whole genomes from non-affected individuals demonstrated a range of 8-120 repeats, with a median of 8.; Changed publications: 17236128, 33510257
Vascular Malformations_Germline v1.4 ARL6IP6 Bryony Thompson Marked gene: ARL6IP6 as ready
Vascular Malformations_Germline v1.4 ARL6IP6 Bryony Thompson Gene: arl6ip6 has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v1.4 ARL6IP6 Bryony Thompson gene: ARL6IP6 was added
gene: ARL6IP6 was added to Vascular Malformations_Germline. Sources: Other
Mode of inheritance for gene: ARL6IP6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARL6IP6 were set to 31142202
Phenotypes for gene: ARL6IP6 were set to Cutis marmorata telangiectatica congenita
Review for gene: ARL6IP6 was set to RED
Added comment: A single case reported from a consanguineous family with a homozygous nonsense variant (p.Trp64Ter).
Sources: Other
Differences of Sex Development v0.215 CPE Zornitza Stark Marked gene: CPE as ready
Differences of Sex Development v0.215 CPE Zornitza Stark Gene: cpe has been classified as Green List (High Evidence).
Differences of Sex Development v0.215 CPE Zornitza Stark Classified gene: CPE as Green List (high evidence)
Differences of Sex Development v0.215 CPE Zornitza Stark Gene: cpe has been classified as Green List (High Evidence).
Differences of Sex Development v0.214 CPE Zornitza Stark gene: CPE was added
gene: CPE was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: CPE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPE were set to 26120850; 32936766; 34383079
Phenotypes for gene: CPE were set to Intellectual developmental disorder and hypogonadotropic hypogonadism, MIM# 619326
Review for gene: CPE was set to GREEN
Added comment: 8 individuals from 5 unrelated families reported.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4150 CPE Zornitza Stark Publications for gene: CPE were set to 26120850; 32936766
Intellectual disability syndromic and non-syndromic v0.4149 CPE Zornitza Stark Classified gene: CPE as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4149 CPE Zornitza Stark Gene: cpe has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4148 CPE Zornitza Stark edited their review of gene: CPE: Added comment: Bosch et al. 2021 (PMID: 34383079) reported on 4 individuals from 3 additional families harbouring 2 different homozygous truncating variants in this gene. Clinical presentation was prominent for obesity and intellectual disability. Hypogonadotropic hypogonadism was confirmed in one individual and was suspected but not tested for in another two subjects.; Changed rating: GREEN; Changed publications: 26120850, 32936766, 34383079; Changed phenotypes: Intellectual developmental disorder and hypogonadotropic hypogonadism, MIM# 619326
Mendeliome v0.9272 CPE Zornitza Stark Publications for gene: CPE were set to 26120850; 32936766
Mendeliome v0.9271 CPE Zornitza Stark Classified gene: CPE as Green List (high evidence)
Mendeliome v0.9271 CPE Zornitza Stark Gene: cpe has been classified as Green List (High Evidence).
Mendeliome v0.9270 CPE Arina Puzriakova reviewed gene: CPE: Rating: GREEN; Mode of pathogenicity: None; Publications: 34383079; Phenotypes: Intellectual developmental disorder and hypogonadotropic hypogonadism, OMIM:619326; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Callosome v0.324 HCFC1 Zornitza Stark Marked gene: HCFC1 as ready
Callosome v0.324 HCFC1 Zornitza Stark Gene: hcfc1 has been classified as Red List (Low Evidence).
Callosome v0.324 HCFC1 Zornitza Stark Phenotypes for gene: HCFC1 were changed from to Mental retardation, X-linked 3 (methylmalonic acidaemia and homocysteinaemia, cblX type) MIM# 309541
Callosome v0.323 HCFC1 Zornitza Stark Publications for gene: HCFC1 were set to
Callosome v0.322 HCFC1 Zornitza Stark Mode of inheritance for gene: HCFC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Callosome v0.321 HCFC1 Zornitza Stark Classified gene: HCFC1 as Red List (low evidence)
Callosome v0.321 HCFC1 Zornitza Stark Gene: hcfc1 has been classified as Red List (Low Evidence).
Callosome v0.320 HCFC1 Zornitza Stark reviewed gene: HCFC1: Rating: RED; Mode of pathogenicity: None; Publications: 34164576, 24011988, 31207118; Phenotypes: Mental retardation, X-linked 3 (methylmalonic acidaemia and homocysteinaemia, cblX type) MIM# 309541; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4148 HCFC1 Zornitza Stark Marked gene: HCFC1 as ready
Intellectual disability syndromic and non-syndromic v0.4148 HCFC1 Zornitza Stark Gene: hcfc1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4148 HCFC1 Zornitza Stark Phenotypes for gene: HCFC1 were changed from to Mental retardation, X-linked 3 (methylmalonic acidaemia and homocysteinaemia, cblX type) MIM# 309541
Intellectual disability syndromic and non-syndromic v0.4147 HCFC1 Zornitza Stark Publications for gene: HCFC1 were set to
Intellectual disability syndromic and non-syndromic v0.4146 HCFC1 Zornitza Stark Mode of inheritance for gene: HCFC1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.4145 HCFC1 Zornitza Stark reviewed gene: HCFC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34164576, 24011988; Phenotypes: Mental retardation, X-linked 3 (methylmalonic acidaemia and homocysteinaemia, cblX type) MIM# 309541; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic Epilepsy v0.1245 HCFC1 Zornitza Stark Marked gene: HCFC1 as ready
Genetic Epilepsy v0.1245 HCFC1 Zornitza Stark Gene: hcfc1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1245 HCFC1 Zornitza Stark Phenotypes for gene: HCFC1 were changed from to Mental retardation, X-linked 3 (methylmalonic acidaemia and homocysteinaemia, cblX type) MIM# 309541
Genetic Epilepsy v0.1244 HCFC1 Zornitza Stark Publications for gene: HCFC1 were set to
Genetic Epilepsy v0.1243 HCFC1 Zornitza Stark Mode of inheritance for gene: HCFC1 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic Epilepsy v0.1243 HCFC1 Zornitza Stark Mode of inheritance for gene: HCFC1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic Epilepsy v0.1242 EIF2S3 Zornitza Stark Marked gene: EIF2S3 as ready
Genetic Epilepsy v0.1242 EIF2S3 Zornitza Stark Gene: eif2s3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1242 EIF2S3 Zornitza Stark Phenotypes for gene: EIF2S3 were changed from to MEHMO syndrome MIM# 300148
Genetic Epilepsy v0.1241 EIF2S3 Zornitza Stark Publications for gene: EIF2S3 were set to
Genetic Epilepsy v0.1240 EIF2S3 Zornitza Stark Mode of inheritance for gene: EIF2S3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic Epilepsy v0.1239 HCFC1 Danielle Ariti changed review comment from: Well-established gene-disease association with >20 individuals reported

Variants in the HCFC1 gene are associated with cases of syndromic and non-syndromic intellectual disability. Individuals present with severely delayed psychomotor development apparent in infancy, and severe neurological defects including intractable epilepsy, facial dysmorphia, and intellectual disability.; to: Well-established gene-disease association with >20 individuals reported

Variants in the HCFC1 gene are associated with cases of syndromic and non-syndromic intellectual disability. Individuals present with severely delayed psychomotor development apparent in infancy, and severe neurological defects including intractable epilepsy, facial dysmorphia, and intellectual disability.
Seizures being a prominent feature in this phenotype.
Genetic Epilepsy v0.1239 HCFC1 Danielle Ariti reviewed gene: HCFC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34164576, 24011988; Phenotypes: Mental retardation, X-linked 3 (methylmalonic acidemia and homocysteinemia, cblX type) MIM# 309541; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic Epilepsy v0.1239 EIF2S3 Danielle Ariti changed review comment from: 7 families reported males with hemizygous EIF2S3 variants; one mouse model.

EIF2S3 variants cause intellectual disability syndrome, MEHMO which is derived from the clinical hallmarks: mental retardation, epileptic seizures, hypogonadism and hypogenitalism, microcephaly, and obesity.
Seizures are prominent within this phenotype (more than 60% of patients).; to: 7 families reported males with hemizygous EIF2S3 variants; one mouse model.

EIF2S3 variants cause intellectual disability syndrome, MEHMO which is derived from the clinical hallmarks: mental retardation, epileptic seizures, hypogonadism and hypogenitalism, microcephaly, and obesity.
Seizures are prominent within this phenotype.
Genetic Epilepsy v0.1239 EIF2S3 Danielle Ariti reviewed gene: EIF2S3: Rating: GREEN; Mode of pathogenicity: None; Publications: 33714664, 32799315, 28055140; Phenotypes: MEHMO syndrome MIM# 300148; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Regression v0.377 CSTB Zornitza Stark Marked gene: CSTB as ready
Regression v0.377 CSTB Zornitza Stark Gene: cstb has been classified as Green List (High Evidence).
Regression v0.377 CSTB Zornitza Stark Classified gene: CSTB as Green List (high evidence)
Regression v0.377 CSTB Zornitza Stark Gene: cstb has been classified as Green List (High Evidence).
Regression v0.376 CSTB Zornitza Stark Tag 5'UTR tag was added to gene: CSTB.
Tag STR tag was added to gene: CSTB.
Regression v0.376 CSTB Zornitza Stark gene: CSTB was added
gene: CSTB was added to Regression. Sources: Expert Review
Mode of inheritance for gene: CSTB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSTB were set to 9012407; 9054946
Phenotypes for gene: CSTB were set to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), MIM# 254800
Review for gene: CSTB was set to GREEN
Added comment: Myoclonic epilepsy of Unverricht and Lundborg is an autosomal recessive disorder characterized by onset of neurodegeneration between 6 and 13 years of age. It is typically progressive in adolescence, with dramatic worsening of myoclonus and ataxia in the first 6 years after onset. The disease stabilises in early adulthood, and myoclonus and ataxia may even improve, and there is minimal to no cognitive decline.

Note the most common causative allele is a dodecamer repeat in the promoter region. Missense variants have been reported, most commonly compound het with the repeat, except for p.Gly4Arg which has been reported in the homozygous state also.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.4145 CSTB Zornitza Stark Marked gene: CSTB as ready
Intellectual disability syndromic and non-syndromic v0.4145 CSTB Zornitza Stark Gene: cstb has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.4145 CSTB Zornitza Stark Phenotypes for gene: CSTB were changed from to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), MIM# 254800
Intellectual disability syndromic and non-syndromic v0.4144 CSTB Zornitza Stark Publications for gene: CSTB were set to
Intellectual disability syndromic and non-syndromic v0.4143 CSTB Zornitza Stark Mode of inheritance for gene: CSTB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4142 CSTB Zornitza Stark Classified gene: CSTB as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.4142 CSTB Zornitza Stark Gene: cstb has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.4141 CSTB Zornitza Stark reviewed gene: CSTB: Rating: RED; Mode of pathogenicity: None; Publications: 9012407, 9054946; Phenotypes: Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), MIM# 254800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9270 CSTB Zornitza Stark Marked gene: CSTB as ready
Mendeliome v0.9270 CSTB Zornitza Stark Gene: cstb has been classified as Green List (High Evidence).
Mendeliome v0.9270 CSTB Zornitza Stark Phenotypes for gene: CSTB were changed from to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) MIM# 254800; Keratolytic winter erythema (MIM#148370)
Mendeliome v0.9269 CSTB Zornitza Stark Publications for gene: CSTB were set to
Mendeliome v0.9268 CSTB Zornitza Stark Mode of inheritance for gene: CSTB was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9267 CSTB Zornitza Stark reviewed gene: CSTB: Rating: GREEN; Mode of pathogenicity: None; Publications: 32920378, 18028412, 9012407, 9054946; Phenotypes: Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) MIM# 254800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.1239 CSTB Zornitza Stark Marked gene: CSTB as ready
Genetic Epilepsy v0.1239 CSTB Zornitza Stark Added comment: Comment when marking as ready: Note the most common causative allele is a dodecamer repeat in the promoter region. Missense variants have been reported, most commonly compound het with the repeat, except for p.Gly4Arg which has been reported in the homozygous state also.
Genetic Epilepsy v0.1239 CSTB Zornitza Stark Gene: cstb has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1239 CSTB Zornitza Stark Tag 5'UTR tag was added to gene: CSTB.
Tag STR tag was added to gene: CSTB.
Genetic Epilepsy v0.1239 CSTB Zornitza Stark Phenotypes for gene: CSTB were changed from Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) MIM# 254800 to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) MIM# 254800
Genetic Epilepsy v0.1238 CSTB Zornitza Stark Phenotypes for gene: CSTB were changed from to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) MIM# 254800
Genetic Epilepsy v0.1237 CSTB Zornitza Stark Publications for gene: CSTB were set to
Genetic Epilepsy v0.1236 CSTB Zornitza Stark Mode of inheritance for gene: CSTB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9267 CD3E Zornitza Stark Marked gene: CD3E as ready
Mendeliome v0.9267 CD3E Zornitza Stark Gene: cd3e has been classified as Green List (High Evidence).
Mendeliome v0.9267 CD3E Zornitza Stark Phenotypes for gene: CD3E were changed from to Immunodeficiency 18 MIM# 615615
Mendeliome v0.9266 CD3E Zornitza Stark Publications for gene: CD3E were set to
Mendeliome v0.9265 CD3E Zornitza Stark Mode of inheritance for gene: CD3E was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Severe Combined Immunodeficiency v0.34 CD3E Zornitza Stark Marked gene: CD3E as ready
Severe Combined Immunodeficiency v0.34 CD3E Zornitza Stark Gene: cd3e has been classified as Green List (High Evidence).
Severe Combined Immunodeficiency v0.34 CD3E Zornitza Stark Phenotypes for gene: CD3E were changed from to Immunodeficiency 18 MIM# 615615
Severe Combined Immunodeficiency v0.33 CD3E Zornitza Stark Publications for gene: CD3E were set to
Severe Combined Immunodeficiency v0.32 CD3E Zornitza Stark Mode of inheritance for gene: CD3E was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9264 CD3D Zornitza Stark Marked gene: CD3D as ready
Mendeliome v0.9264 CD3D Zornitza Stark Gene: cd3d has been classified as Green List (High Evidence).
Mendeliome v0.9264 CD3D Zornitza Stark Phenotypes for gene: CD3D were changed from to Immunodeficiency 19 MIM# 615617
Mendeliome v0.9263 CD3D Zornitza Stark Publications for gene: CD3D were set to
Mendeliome v0.9262 CD3D Zornitza Stark Mode of inheritance for gene: CD3D was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Severe Combined Immunodeficiency v0.31 CD3D Zornitza Stark Marked gene: CD3D as ready
Severe Combined Immunodeficiency v0.31 CD3D Zornitza Stark Gene: cd3d has been classified as Green List (High Evidence).
Severe Combined Immunodeficiency v0.31 CD3D Zornitza Stark Phenotypes for gene: CD3D were changed from to Immunodeficiency 19 MIM# 615617
Severe Combined Immunodeficiency v0.30 CD3D Zornitza Stark Publications for gene: CD3D were set to
Severe Combined Immunodeficiency v0.29 CD3D Zornitza Stark Mode of inheritance for gene: CD3D was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9261 ARHGAP26 Zornitza Stark Marked gene: ARHGAP26 as ready
Mendeliome v0.9261 ARHGAP26 Zornitza Stark Gene: arhgap26 has been classified as Red List (Low Evidence).
Mendeliome v0.9261 ARHGAP26 Zornitza Stark Classified gene: ARHGAP26 as Red List (low evidence)
Mendeliome v0.9261 ARHGAP26 Zornitza Stark Gene: arhgap26 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1235 CSTB Danielle Ariti reviewed gene: CSTB: Rating: GREEN; Mode of pathogenicity: None; Publications: 32920378, 18028412; Phenotypes: Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) MIM# 254800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v0.165 SCN8A Zornitza Stark Marked gene: SCN8A as ready
Cerebral Palsy v0.165 SCN8A Zornitza Stark Gene: scn8a has been classified as Green List (High Evidence).
Cerebral Palsy v0.165 SCN8A Zornitza Stark Phenotypes for gene: SCN8A were changed from to Cerebral Palsy; Epileptic encephalopathy 13 MIM# 614558; Cognitive impairment with or without cerebellar ataxia MIM# 614306
Cerebral Palsy v0.164 SCN8A Zornitza Stark Publications for gene: SCN8A were set to
Cerebral Palsy v0.163 SCN8A Zornitza Stark Mode of inheritance for gene: SCN8A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9260 LEFTY2 Zornitza Stark Marked gene: LEFTY2 as ready
Mendeliome v0.9260 LEFTY2 Zornitza Stark Added comment: Comment when marking as ready: No reports since 1999.
Mendeliome v0.9260 LEFTY2 Zornitza Stark Gene: lefty2 has been classified as Red List (Low Evidence).
Mendeliome v0.9260 LEFTY2 Zornitza Stark Phenotypes for gene: LEFTY2 were changed from to Heterotaxy
Mendeliome v0.9259 LEFTY2 Zornitza Stark Publications for gene: LEFTY2 were set to
Mendeliome v0.9258 LEFTY2 Zornitza Stark Mode of inheritance for gene: LEFTY2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9257 LEFTY2 Zornitza Stark Classified gene: LEFTY2 as Red List (low evidence)
Mendeliome v0.9257 LEFTY2 Zornitza Stark Gene: lefty2 has been classified as Red List (Low Evidence).
Mendeliome v0.9256 CD3E Danielle Ariti reviewed gene: CD3E: Rating: GREEN; Mode of pathogenicity: None; Publications: 5546002, 28597365, 8490660; Phenotypes: Immunodeficiency 18 MIM# 615615; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe Combined Immunodeficiency v0.28 CD3E Danielle Ariti reviewed gene: CD3E: Rating: GREEN; Mode of pathogenicity: None; Publications: 15546002, 28597365, 8490660; Phenotypes: Immunodeficiency 18 MIM# 615615; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9256 CD3D Danielle Ariti reviewed gene: CD3D: Rating: GREEN; Mode of pathogenicity: None; Publications: 14602880, 15546002, 21926461, 21883749; Phenotypes: Immunodeficiency 19 MIM# 615617; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe Combined Immunodeficiency v0.28 CD3D Danielle Ariti reviewed gene: CD3D: Rating: GREEN; Mode of pathogenicity: None; Publications: 14602880, 15546002, 21926461, 21883749; Phenotypes: Immunodeficiency 19 MIM# 615617; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9256 ARHGAP26 Dean Phelan reviewed gene: ARHGAP26: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: Unknown
Cerebral Palsy v0.162 SCN8A Danielle Ariti reviewed gene: SCN8A: Rating: GREEN; Mode of pathogenicity: Other; Publications: 33528536, 32989326, 31904124; Phenotypes: Cerebral Palsy, Epileptic encephalopathy 13 MIM# 614558, Cognitive impairment with or without cerebellar ataxia MIM# 614306; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9256 MPL Zornitza Stark Phenotypes for gene: MPL were changed from Myelofibrosis with myeloid metaplasia, somatic, MIM#2544503; Thrombocythemia 2, MIM#601977, AD, SMu; Thrombocytopenia, congenital amegakaryocytic, MIM#604498, AR to Myelofibrosis with myeloid metaplasia, somatic, MIM#254450; Thrombocythemia 2, MIM#601977, AD, SMu; Thrombocytopenia, congenital amegakaryocytic, MIM#604498, AR
Bone Marrow Failure v1.7 MPL Zornitza Stark Phenotypes for gene: MPL were changed from Myelofibrosis with myeloid metaplasia, somatic, MIM#2544503; Thrombocythemia 2, MIM#601977, AD, SMu; Thrombocytopenia, congenital amegakaryocytic, MIM#604498, AR to Myelofibrosis with myeloid metaplasia, somatic, MIM#254450; Thrombocythemia 2, MIM#601977, AD, SMu; Thrombocytopenia, congenital amegakaryocytic, MIM#604498, AR
Bone Marrow Failure v1.6 MPL Zornitza Stark edited their review of gene: MPL: Changed phenotypes: Myelofibrosis with myeloid metaplasia, somatic, MIM#254450, Thrombocythemia 2, MIM#601977, AD, SMu, Thrombocytopenia, congenital amegakaryocytic, MIM#604498, AR
Additional findings_Paediatric v0.257 PTPRC Zornitza Stark Phenotypes for gene: PTPRC were changed from Severe combined immunodeficiency, T cell-negative, B-cell/natural killer-cell positive MIM# 151460 to Severe combined immunodeficiency, T cell-negative, B-cell/natural killer-cell positive MIM# 608971
Mendeliome v0.9255 EPAS1 Zornitza Stark Phenotypes for gene: EPAS1 were changed from Familial erythrocytosis (MIM#4611783), AD to Familial erythrocytosis (MIM#611783), AD
Liver Failure_Paediatric v1.8 BCS1L Zornitza Stark Phenotypes for gene: BCS1L were changed from GRACILE syndrome, MIM# 603358; Mitochondrial complex III deficiency, nuclear type 1 , MIM#124000 to GRACILE syndrome, MIM# 603358; Mitochondrial complex III deficiency, nuclear type 1 , MIM#112400
Liver Failure_Paediatric v1.7 BCS1L Zornitza Stark edited their review of gene: BCS1L: Changed phenotypes: GRACILE syndrome, MIM# 603358, Mitochondrial complex III deficiency, nuclear type 1 , MIM#112400
Mendeliome v0.9254 BCS1L Zornitza Stark Phenotypes for gene: BCS1L were changed from Bjornstad syndrome MIM#262000; GRACILE syndrome, MIM#603358; Mitochondrial complex III deficiency, nuclear type MIM#1124000 to Bjornstad syndrome MIM#262000; GRACILE syndrome, MIM#603358; Mitochondrial complex III deficiency, nuclear type MIM#112400
Cholestasis v0.204 BCS1L Zornitza Stark Phenotypes for gene: BCS1L were changed from GRACILE syndrome, MIM# 603358; Mitochondrial complex III deficiency, nuclear type 1 , MIM#124000 to GRACILE syndrome, MIM# 603358; Mitochondrial complex III deficiency, nuclear type 1 , MIM#112400
Cholestasis v0.203 BCS1L Zornitza Stark edited their review of gene: BCS1L: Changed phenotypes: GRACILE syndrome, MIM# 603358, Mitochondrial complex III deficiency, nuclear type 1 , MIM#112400
Cholestasis v0.203 BCS1L Zornitza Stark edited their review of gene: BCS1L: Changed phenotypes: GRACILE syndrome, MIM# 603358, Mitochondrial complex III deficiency, nuclear type 1 , MIM#12400
Mendeliome v0.9253 OPA1 Zornitza Stark Phenotypes for gene: OPA1 were changed from Mitochondrial DNA depletion syndrome 14 (encephalocardiomyopathic type)MIM# 6168963; Behr syndrome MIM#210000, AR; Optic atrophy 1, MIM#165500; Optic atrophy plus syndrome, MIM# 125250 to Mitochondrial DNA depletion syndrome 14 (encephalocardiomyopathic type)MIM# 616896; Behr syndrome MIM#210000, AR; Optic atrophy 1, MIM#165500; Optic atrophy plus syndrome, MIM# 125250
Cerebral Palsy v0.162 MECP2 Zornitza Stark Marked gene: MECP2 as ready
Cerebral Palsy v0.162 MECP2 Zornitza Stark Gene: mecp2 has been classified as Green List (High Evidence).
Cerebral Palsy v0.162 MECP2 Zornitza Stark Classified gene: MECP2 as Green List (high evidence)
Cerebral Palsy v0.162 MECP2 Zornitza Stark Gene: mecp2 has been classified as Green List (High Evidence).
Mendeliome v0.9252 MAOB Zornitza Stark Marked gene: MAOB as ready
Mendeliome v0.9252 MAOB Zornitza Stark Gene: maob has been classified as Red List (Low Evidence).
Mendeliome v0.9252 MAOB Zornitza Stark gene: MAOB was added
gene: MAOB was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: MAOB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAOB were set to 31700678
Phenotypes for gene: MAOB were set to Cerebral palsy
Review for gene: MAOB was set to RED
Added comment: Variants identified in 2 unrelated individuals with CP (with same variant also identified in unaffected monozygotic twin).
Sources: Expert Review
Cerebral Palsy v0.161 MFN2 Krithika Murali gene: MFN2 was added
gene: MFN2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MFN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MFN2 were set to 16437557; 21715711; 34114234; 33528536
Phenotypes for gene: MFN2 were set to Charcot-Marie-Tooth disease, axonal, type 2A2A - #609260; Charcot-Marie-Tooth disease, axonal, type 2A2B - #617087; Hereditary motor and sensory neuropathy VIA - 601152
Review for gene: MFN2 was set to RED
Added comment: Most common cause of axonal Charcot-Marie-Tooth disease (CMT2). Homozygous and compound heterozygous MFN2 mutations have been reported in early-onset CMT2, including patients diagnosed <12 months of age.

x1 het VUS reported in a prematurely born child with unilateral spastic CP (34114234)
x1 paternally inherited pathogenic variant in MFN2 reported in 1 patient in CP cohort (33528536)
Sources: Literature
Cerebral Palsy v0.161 MAOB Zornitza Stark Marked gene: MAOB as ready
Cerebral Palsy v0.161 MAOB Zornitza Stark Gene: maob has been classified as Red List (Low Evidence).
Cerebral Palsy v0.161 MAOB Zornitza Stark Phenotypes for gene: MAOB were changed from to Cerebral palsy
Cerebral Palsy v0.160 MAOB Zornitza Stark Classified gene: MAOB as Red List (low evidence)
Cerebral Palsy v0.160 MAOB Zornitza Stark Gene: maob has been classified as Red List (Low Evidence).
Cerebral Palsy v0.159 KMT2B Zornitza Stark Marked gene: KMT2B as ready
Cerebral Palsy v0.159 KMT2B Zornitza Stark Gene: kmt2b has been classified as Red List (Low Evidence).
Cerebral Palsy v0.159 KMT2B Zornitza Stark Classified gene: KMT2B as Red List (low evidence)
Cerebral Palsy v0.159 KMT2B Zornitza Stark Gene: kmt2b has been classified as Red List (Low Evidence).
Cerebral Palsy v0.158 KMT2A Zornitza Stark Marked gene: KMT2A as ready
Cerebral Palsy v0.158 KMT2A Zornitza Stark Gene: kmt2a has been classified as Green List (High Evidence).
Cerebral Palsy v0.158 KMT2A Zornitza Stark Classified gene: KMT2A as Green List (high evidence)
Cerebral Palsy v0.158 KMT2A Zornitza Stark Gene: kmt2a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1235 KDM5C Zornitza Stark Marked gene: KDM5C as ready
Genetic Epilepsy v0.1235 KDM5C Zornitza Stark Gene: kdm5c has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1235 KDM5C Zornitza Stark Phenotypes for gene: KDM5C were changed from Epilepsy; Intellectual Disability; microcephaly; Spasticity; hypothyroidism to Epilepsy; Intellectual Disability; microcephaly; Spasticity; hypothyroidism; Mental retardation, X-linked, syndromic, Claes-Jensen type, MIM# 300534; MONDO:0010355
Genetic Epilepsy v0.1234 KDM5C Zornitza Stark Publications for gene: KDM5C were set to 23246292; 32279304; 26919706
Genetic Epilepsy v0.1233 KDM5C Zornitza Stark Classified gene: KDM5C as Green List (high evidence)
Genetic Epilepsy v0.1233 KDM5C Zornitza Stark Gene: kdm5c has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1232 KDM5C Zornitza Stark reviewed gene: KDM5C: Rating: GREEN; Mode of pathogenicity: None; Publications: 15586325, 32279304; Phenotypes: Mental retardation, X-linked, syndromic, Claes-Jensen type, MIM# 300534, MONDO:0010355; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic Epilepsy v0.1232 ATP6V1B2 Zornitza Stark Marked gene: ATP6V1B2 as ready
Genetic Epilepsy v0.1232 ATP6V1B2 Zornitza Stark Gene: atp6v1b2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1232 ATP6V1B2 Zornitza Stark Classified gene: ATP6V1B2 as Green List (high evidence)
Genetic Epilepsy v0.1232 ATP6V1B2 Zornitza Stark Gene: atp6v1b2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1231 ATP6V1B2 Zornitza Stark reviewed gene: ATP6V1B2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32873933; Phenotypes: Epileptic encephalopathy, Intellectual Disability, Deafness, congenital, with onychodystrophy, autosomal dominant, MIM# 124480; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4141 ATP6V0C Zornitza Stark Marked gene: ATP6V0C as ready
Intellectual disability syndromic and non-syndromic v0.4141 ATP6V0C Zornitza Stark Gene: atp6v0c has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4141 ATP6V0C Zornitza Stark Classified gene: ATP6V0C as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.4141 ATP6V0C Zornitza Stark Gene: atp6v0c has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4140 ATP6V0C Zornitza Stark gene: ATP6V0C was added
gene: ATP6V0C was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
SV/CNV tags were added to gene: ATP6V0C.
Mode of inheritance for gene: ATP6V0C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP6V0C were set to 33190975; 33090716
Phenotypes for gene: ATP6V0C were set to Epilepsy; Intellectual Disability; microcephaly
Review for gene: ATP6V0C was set to AMBER
Added comment: 9 individuals reported with deletions and ID/seizures/microcephaly, minimum overlapping region implicates ATP6V0C as the causative gene. Single case report of de novo SNV and ID/seizures.
Sources: Literature
Mendeliome v0.9251 ATP6V0C Zornitza Stark Marked gene: ATP6V0C as ready
Mendeliome v0.9251 ATP6V0C Zornitza Stark Gene: atp6v0c has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9251 ATP6V0C Zornitza Stark Classified gene: ATP6V0C as Amber List (moderate evidence)
Mendeliome v0.9251 ATP6V0C Zornitza Stark Gene: atp6v0c has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9250 ATP6V0C Zornitza Stark Tag SV/CNV tag was added to gene: ATP6V0C.
Mendeliome v0.9250 ATP6V0C Zornitza Stark gene: ATP6V0C was added
gene: ATP6V0C was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATP6V0C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP6V0C were set to 33190975; 33090716
Phenotypes for gene: ATP6V0C were set to Epilepsy; Intellectual Disability; microcephaly
Review for gene: ATP6V0C was set to AMBER
Added comment: 9 individuals reported with deletions and ID/seizures/microcephaly, minimum overlapping region implicates ATP6V0C as the causative gene. Single case report of de novo SNV and ID/seizures.
Sources: Literature
Genetic Epilepsy v0.1231 ATP6V0C Zornitza Stark Marked gene: ATP6V0C as ready
Genetic Epilepsy v0.1231 ATP6V0C Zornitza Stark Gene: atp6v0c has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1231 ATP6V0C Zornitza Stark Classified gene: ATP6V0C as Amber List (moderate evidence)
Genetic Epilepsy v0.1231 ATP6V0C Zornitza Stark Gene: atp6v0c has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1230 ATP6V0C Zornitza Stark Tag SV/CNV tag was added to gene: ATP6V0C.
Genetic Epilepsy v0.1230 ATP6V0C Zornitza Stark reviewed gene: ATP6V0C: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual disability, seizures; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v0.157 MECP2 Krithika Murali gene: MECP2 was added
gene: MECP2 was added to Cerebral Palsy. Sources: Expert list,Literature
Mode of inheritance for gene: MECP2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: MECP2 were set to 30542205; 33528536
Phenotypes for gene: MECP2 were set to Encephalopathy, neonatal severe - 300673; Intellectual developmental disorder, X-linked syndromic, Lubs type - 300260; Intellectual developmental disorder, X-linked, syndromic 13 - 300055; Rett syndrome - 312750
Review for gene: MECP2 was set to GREEN
Added comment: Pathogenic/likely pathogenic variants reported in 9 unrelated patients with CP
Sources: Expert list, Literature
Cerebral Palsy v0.157 MAOB Krithika Murali gene: MAOB was added
gene: MAOB was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MAOB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAOB were set to 31700678
Review for gene: MAOB was set to RED
Added comment: Identified in 2 unrelated individuals with CP (with same variant also identified in unaffected monozygotic twin) in a gene not currently known to be associated disease.
Sources: Literature
Cerebral Palsy v0.157 KMT2B Krithika Murali gene: KMT2B was added
gene: KMT2B was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KMT2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KMT2B were set to 29697234
Phenotypes for gene: KMT2B were set to Dystonia 28, childhood-onset - #617284
Review for gene: KMT2B was set to RED
Added comment: Progressive early-onset movement disorder (mean age 7 years). Variants not previously reported in patients with CP.
Sources: Literature
Cerebral Palsy v0.157 KMT2A Krithika Murali gene: KMT2A was added
gene: KMT2A was added to Cerebral Palsy. Sources: Expert list,Literature
Mode of inheritance for gene: KMT2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KMT2A were set to 33528536
Phenotypes for gene: KMT2A were set to Wiedemann-Steiner syndrome - #605130
Review for gene: KMT2A was set to GREEN
Added comment: Pathogenic/likely pathogenic variants identified in 5 unrelated patients with CP (Moreno-de-Luca et al 2021).
Sources: Expert list, Literature
Genetic Epilepsy v0.1230 KDM5C Kavitha Kothur gene: KDM5C was added
gene: KDM5C was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KDM5C was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: KDM5C were set to 23246292; 32279304; 26919706
Phenotypes for gene: KDM5C were set to Epilepsy; Intellectual Disability; microcephaly; Spasticity; hypothyroidism
Genetic Epilepsy v0.1230 ATP6V1B2 Kavitha Kothur gene: ATP6V1B2 was added
gene: ATP6V1B2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ATP6V1B2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP6V1B2 were set to 31655144; 32934366; 32597767
Phenotypes for gene: ATP6V1B2 were set to Epileptic encephalopathy; Intellectual Disability; microcephaly, DOORS syndrome
Review for gene: ATP6V1B2 was set to GREEN
Added comment: Sources: Literature
Genetic Epilepsy v0.1230 ATP6V0C Kavitha Kothur gene: ATP6V0C was added
gene: ATP6V0C was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ATP6V0C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP6V0C were set to 33190975; 33090716
Phenotypes for gene: ATP6V0C were set to Epilepsy; Intellectual Disability; microcephaly
Penetrance for gene: ATP6V0C were set to unknown
Review for gene: ATP6V0C was set to AMBER
Added comment: Sources: Literature
Cerebral Palsy v0.157 KIDINS220 Zornitza Stark Marked gene: KIDINS220 as ready
Cerebral Palsy v0.157 KIDINS220 Zornitza Stark Added comment: Comment when marking as ready: Phenotypic overlap with CP particularly for mono-allelic disease association.
Cerebral Palsy v0.157 KIDINS220 Zornitza Stark Gene: kidins220 has been classified as Green List (High Evidence).
Cerebral Palsy v0.157 KIDINS220 Zornitza Stark Classified gene: KIDINS220 as Green List (high evidence)
Cerebral Palsy v0.157 KIDINS220 Zornitza Stark Gene: kidins220 has been classified as Green List (High Evidence).
Cerebral Palsy v0.156 KIDINS220 Krithika Murali gene: KIDINS220 was added
gene: KIDINS220 was added to Cerebral Palsy. Sources: Expert list,Literature
Mode of inheritance for gene: KIDINS220 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIDINS220 were set to 30542205
Phenotypes for gene: KIDINS220 were set to Spastic paraplegia, intellectual disability, nystagmus, and obesity - #617296; Ventriculomegaly and arthrogryposis - #619501
Review for gene: KIDINS220 was set to GREEN
Added comment: Well-established association with AD spastic paraplegia and AR ventriculomegaly and arthrogryposis - phenotypic overlap noted with CP.

Also reported in 2 siblings with atypical CP likely due to parental germline mosaicism (PMID 30542205)

Alternative gene names: ARMS
Sources: Expert list, Literature
Mendeliome v0.9249 KDM7A Zornitza Stark Marked gene: KDM7A as ready
Mendeliome v0.9249 KDM7A Zornitza Stark Gene: kdm7a has been classified as Red List (Low Evidence).
Mendeliome v0.9249 KDM7A Zornitza Stark gene: KDM7A was added
gene: KDM7A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KDM7A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KDM7A were set to 25666757
Phenotypes for gene: KDM7A were set to Cerebral palsy
Review for gene: KDM7A was set to RED
Added comment: Synonyms: JHDMID, KDM7, KIAA1718

De novo missense VUS identified in a WES CP cohort study, no other reports.
Sources: Literature
Cerebral Palsy v0.156 KDM7A Zornitza Stark Marked gene: KDM7A as ready
Cerebral Palsy v0.156 KDM7A Zornitza Stark Gene: kdm7a has been classified as Red List (Low Evidence).
Cerebral Palsy v0.156 KDM7A Zornitza Stark Phenotypes for gene: KDM7A were changed from to Cerebral palsy
Cerebral Palsy v0.155 KDM7A Zornitza Stark Classified gene: KDM7A as Red List (low evidence)
Cerebral Palsy v0.155 KDM7A Zornitza Stark Gene: kdm7a has been classified as Red List (Low Evidence).
Cerebral Palsy v0.154 KCNQ2 Zornitza Stark reviewed gene: KCNQ2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 7 - #613720; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v0.154 KCNQ2 Zornitza Stark Marked gene: KCNQ2 as ready
Cerebral Palsy v0.154 KCNQ2 Zornitza Stark Gene: kcnq2 has been classified as Green List (High Evidence).
Cerebral Palsy v0.154 KCNQ2 Zornitza Stark Phenotypes for gene: KCNQ2 were changed from Developmental and epileptic encephalopathy 7 - #613720; Myokymia - #121200; Seizures, benign neonatal, 1 - #121200 to Developmental and epileptic encephalopathy 7 - #613720
Cerebral Palsy v0.153 KCNQ2 Zornitza Stark Classified gene: KCNQ2 as Green List (high evidence)
Cerebral Palsy v0.153 KCNQ2 Zornitza Stark Gene: kcnq2 has been classified as Green List (High Evidence).
Mendeliome v0.9248 ROBO1 Zornitza Stark Marked gene: ROBO1 as ready
Mendeliome v0.9248 ROBO1 Zornitza Stark Gene: robo1 has been classified as Green List (High Evidence).
Mendeliome v0.9248 ROBO1 Zornitza Stark Phenotypes for gene: ROBO1 were changed from to Congenital heart disease; Pituitary anomalies
Mendeliome v0.9247 ROBO1 Zornitza Stark Publications for gene: ROBO1 were set to
Mendeliome v0.9246 ROBO1 Zornitza Stark Mode of inheritance for gene: ROBO1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.9245 ROBO1 Zornitza Stark reviewed gene: ROBO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28592524, 30530901, 30692597, 33270637, 28402530; Phenotypes: Congenital heart disease, Pituitary anomalies; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Pituitary hormone deficiency v0.19 ROBO1 Zornitza Stark Marked gene: ROBO1 as ready
Pituitary hormone deficiency v0.19 ROBO1 Zornitza Stark Gene: robo1 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.19 ROBO1 Zornitza Stark Classified gene: ROBO1 as Green List (high evidence)
Pituitary hormone deficiency v0.19 ROBO1 Zornitza Stark Gene: robo1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.152 KDM7A Krithika Murali changed review comment from: Synonyms: JHDMID, KDM7, KIAA1718

De novo missense VUS identified in a WES CP cohort study in a gene not known to be associated with disease.
Sources: Expert list, Literature; to: Synonyms: JHDMID, KDM7, KIAA1718

De novo missense VUS identified in a WES CP cohort study in a gene not known to be associated with disease.
Sources: Literature
Cerebral Palsy v0.152 KDM7A Krithika Murali gene: KDM7A was added
gene: KDM7A was added to Cerebral Palsy. Sources: Expert list,Literature
Mode of inheritance for gene: KDM7A was set to Unknown
Publications for gene: KDM7A were set to 25666757
Review for gene: KDM7A was set to RED
Added comment: Synonyms: JHDMID, KDM7, KIAA1718

De novo missense VUS identified in a WES CP cohort study in a gene not known to be associated with disease.
Sources: Expert list, Literature
Cerebral Palsy v0.152 KCNQ2 Krithika Murali gene: KCNQ2 was added
gene: KCNQ2 was added to Cerebral Palsy. Sources: Expert list,Literature
Mode of inheritance for gene: KCNQ2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNQ2 were set to 33557955; 32585800; 22275249; 28655139
Phenotypes for gene: KCNQ2 were set to Developmental and epileptic encephalopathy 7 - #613720; Myokymia - #121200; Seizures, benign neonatal, 1 - #121200
Review for gene: KCNQ2 was set to AMBER
Added comment: Well-validated association with early-onset epileptic encephalopathy (ClinGen) and neonatal seizures.


In addition, KCNQ2 pathogenic variants reported in multiple individuals with intractable neonatal seizures and associated intellectual disability, developmental delay and motor impairment (axial hypotonia and/or spastic quadriplegia) - (PMID 22275249)

x2 case reports of associated CP - 6 year old M with neonatal seizures and a CP-like syndrome. KCNQ2 exon 7 partial duplication impairing gene function (ClinVar ID 617505) - (PMID 32585800 and 33557955) and 2 year old F with perinatal encephalopathy, severe tetraparesis and cerebral visual impairment (PMID 28655139). Neonatal epileptic encephalopathy primary presentation in both cases.

On Expert CP Gene List.
Sources: Expert list, Literature
Pituitary hormone deficiency v0.18 ROBO1 Natasha Brown gene: ROBO1 was added
gene: ROBO1 was added to Pituitary hormone deficiency. Sources: Literature
Mode of inheritance for gene: ROBO1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: ROBO1 were set to PMID: 30530901; 30692597; 33270637; 28402530
Phenotypes for gene: ROBO1 were set to pituitary stalk interruption syndrome; pituitary anomalies; pituitary hormone deficiency
Review for gene: ROBO1 was set to GREEN
Added comment: PMID: 30692597 novel hmz splice, single case; severe phenotype combined pituitary hormone deficiency, psychomotor developmental delay, severe intellectual disability, sensorineural hearing loss, strabismus, dysmorphism; parents reported to be unaffected.
PMID: 30530901 Two affected from one family with 343.7 kb deletion of 3p12.3 encompassing ROBO1
PMID: 33270637 Larger cohort study found four individiuals (2x LOF; 2x missense) all het variants however those with missense variants also had other variants in different genes, evidence for pathogenicity of missense variants less clear.
PMID: 28402530 In five unexplained cases of pit stalk interruption, found: p.Ala977Glnfs*40 in two affected sibs; p.Tyr1114Ter in a sporadic case, and p.Cys240Ser, affected child and paternal aunt. All heterozygous.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4139 ARFGEF1 Zornitza Stark Marked gene: ARFGEF1 as ready
Intellectual disability syndromic and non-syndromic v0.4139 ARFGEF1 Zornitza Stark Gene: arfgef1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4139 ARFGEF1 Zornitza Stark Classified gene: ARFGEF1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4139 ARFGEF1 Zornitza Stark Gene: arfgef1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4138 ARFGEF1 Zornitza Stark gene: ARFGEF1 was added
gene: ARFGEF1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ARFGEF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARFGEF1 were set to 34113008
Phenotypes for gene: ARFGEF1 were set to Intellectual disability; Epilepsy
Review for gene: ARFGEF1 was set to GREEN
Added comment: 13 individuals reported with variants in this gene and a neurodevelopmental disorder characterised by variable ID, seizures present in around half. Variants were inherited from mildly affected parents in 40% of families.
Sources: Literature
Genetic Epilepsy v0.1230 ARFGEF1 Zornitza Stark Marked gene: ARFGEF1 as ready
Genetic Epilepsy v0.1230 ARFGEF1 Zornitza Stark Gene: arfgef1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1230 ARFGEF1 Zornitza Stark Classified gene: ARFGEF1 as Green List (high evidence)
Genetic Epilepsy v0.1230 ARFGEF1 Zornitza Stark Gene: arfgef1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1229 ARFGEF1 Zornitza Stark gene: ARFGEF1 was added
gene: ARFGEF1 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: ARFGEF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARFGEF1 were set to 34113008
Phenotypes for gene: ARFGEF1 were set to Intellectual disability; Epilepsy
Review for gene: ARFGEF1 was set to GREEN
Added comment: 13 individuals reported with variants in this gene and a neurodevelopmental disorder characterised by variable ID, seizures present in around half. Variants were inherited from mildly affected parents in 40% of families.
Sources: Expert Review
Mendeliome v0.9245 ARFGEF1 Zornitza Stark Marked gene: ARFGEF1 as ready
Mendeliome v0.9245 ARFGEF1 Zornitza Stark Gene: arfgef1 has been classified as Green List (High Evidence).
Mendeliome v0.9245 ARFGEF1 Zornitza Stark Classified gene: ARFGEF1 as Green List (high evidence)
Mendeliome v0.9245 ARFGEF1 Zornitza Stark Gene: arfgef1 has been classified as Green List (High Evidence).
Mendeliome v0.9244 ARFGEF1 Zornitza Stark gene: ARFGEF1 was added
gene: ARFGEF1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: ARFGEF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARFGEF1 were set to 34113008
Phenotypes for gene: ARFGEF1 were set to Intellectual disability; Epilepsy
Review for gene: ARFGEF1 was set to GREEN
Added comment: 13 individuals reported with variants in this gene and a neurodevelopmental disorder characterised by variable ID, seizures present in around half. Variants were inherited from mildly affected parents in 40% of families.
Sources: Expert Review
Genetic Epilepsy v0.1228 AP4B1 Zornitza Stark Marked gene: AP4B1 as ready
Genetic Epilepsy v0.1228 AP4B1 Zornitza Stark Gene: ap4b1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1228 AP4B1 Zornitza Stark Classified gene: AP4B1 as Green List (high evidence)
Genetic Epilepsy v0.1228 AP4B1 Zornitza Stark Gene: ap4b1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1227 AP4B1 Zornitza Stark gene: AP4B1 was added
gene: AP4B1 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: AP4B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP4B1 were set to 21620353; 22290197; 24700674; 24781758; 32166732
Phenotypes for gene: AP4B1 were set to Spastic paraplegia 47, autosomal recessive, MIM# 614066
Review for gene: AP4B1 was set to GREEN
Added comment: Autosomal recessive neurodegenerative disorder characterised by neonatal hypotonia that progresses to hypertonia and spasticity and severe ID with poor or absent speech development. Microcephaly is an early, presenting feature. Seizures reported in at least 3 families.

>5 unrelated families reported.
Sources: Expert Review
Mendeliome v0.9243 NPR3 Zornitza Stark Marked gene: NPR3 as ready
Mendeliome v0.9243 NPR3 Zornitza Stark Gene: npr3 has been classified as Green List (High Evidence).
Mendeliome v0.9243 NPR3 Zornitza Stark Phenotypes for gene: NPR3 were changed from to Boudin-Mortier syndrome, MIM#619543; Tall stature, skeletal abnormalities, aortic dilatation
Mendeliome v0.9242 NPR3 Zornitza Stark Publications for gene: NPR3 were set to
Mendeliome v0.9241 NPR3 Zornitza Stark Mode of inheritance for gene: NPR3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9240 NPR3 Zornitza Stark reviewed gene: NPR3: Rating: GREEN; Mode of pathogenicity: None; Publications: 30032985; Phenotypes: Boudin-Mortier syndrome, MIM#619543, Tall stature, skeletal abnormalities, aortic dilatation; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v1.55 NPR3 Zornitza Stark Phenotypes for gene: NPR3 were changed from Tall stature, skeletal abnormalities, aortic dilatation to Boudin-Mortier syndrome, MIM#619543; Tall stature, skeletal abnormalities, aortic dilatation
Aortopathy_Connective Tissue Disorders v1.54 NPR3 Zornitza Stark edited their review of gene: NPR3: Changed phenotypes: Boudin-Mortier syndrome, MIM#619543, Tall stature, skeletal abnormalities, aortic dilatation
Intellectual disability syndromic and non-syndromic v0.4137 PRR12 Zornitza Stark Phenotypes for gene: PRR12 were changed from intellectual disability; iris abnormalities to Neuroocular syndrome, MIM#619539; Intellectual disability; Iris abnormalities; Complex microphthalmia
Intellectual disability syndromic and non-syndromic v0.4136 PRR12 Zornitza Stark edited their review of gene: PRR12: Changed phenotypes: Neuroocular syndrome, MIM#619539, Intellectual disability, Iris abnormalities, Complex microphthalmia
Mendeliome v0.9240 PRR12 Zornitza Stark Phenotypes for gene: PRR12 were changed from Intellectual disability; Iris abnormalities; Complex microphthalmia to Neuroocular syndrome, MIM#619539; Intellectual disability; Iris abnormalities; Complex microphthalmia
Mendeliome v0.9239 PRR12 Zornitza Stark edited their review of gene: PRR12: Changed phenotypes: Neuroocular syndrome, MIM#619539, Intellectual disability, Iris abnormalities, Complex microphthalmia
Anophthalmia_Microphthalmia_Coloboma v1.8 PRR12 Zornitza Stark Phenotypes for gene: PRR12 were changed from Complex microphthalmia to Neuroocular syndrome, MIM#619539; Complex microphthalmia
Anophthalmia_Microphthalmia_Coloboma v1.7 PRR12 Zornitza Stark edited their review of gene: PRR12: Changed phenotypes: Neuroocular syndrome, MIM#619539, Complex microphthalmia
Mendeliome v0.9239 KCNC3 Zornitza Stark Marked gene: KCNC3 as ready
Mendeliome v0.9239 KCNC3 Zornitza Stark Gene: kcnc3 has been classified as Green List (High Evidence).
Mendeliome v0.9239 KCNC3 Zornitza Stark Phenotypes for gene: KCNC3 were changed from to Spinocerebellar ataxia 13, MIM# 605259
Mendeliome v0.9238 KCNC3 Zornitza Stark Publications for gene: KCNC3 were set to
Mendeliome v0.9237 KCNC3 Zornitza Stark Mode of inheritance for gene: KCNC3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9236 KCNC3 Zornitza Stark reviewed gene: KCNC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 16501573, 25497598, 25981959, 25981959; Phenotypes: Spinocerebellar ataxia 13, MIM# 605259; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v0.152 KCNC3 Zornitza Stark Marked gene: KCNC3 as ready
Cerebral Palsy v0.152 KCNC3 Zornitza Stark Gene: kcnc3 has been classified as Green List (High Evidence).
Cerebral Palsy v0.152 KCNC3 Zornitza Stark Classified gene: KCNC3 as Green List (high evidence)
Cerebral Palsy v0.152 KCNC3 Zornitza Stark Gene: kcnc3 has been classified as Green List (High Evidence).
Cerebral Palsy v0.151 KCNC3 Zornitza Stark gene: KCNC3 was added
gene: KCNC3 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: KCNC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNC3 were set to 16501573; 25497598; 25981959; 25981959
Phenotypes for gene: KCNC3 were set to Spinocerebellar ataxia 13, MIM# 605259
Review for gene: KCNC3 was set to GREEN
Added comment: ID and ataxia, variable age of onset, including in childhood. Reported in ataxic CP cohort.
Sources: Expert list
Cerebral Palsy v0.151 KCNC3 Zornitza Stark gene: KCNC3 was added
gene: KCNC3 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: KCNC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNC3 were set to 16501573; 25497598; 25981959; 25981959
Phenotypes for gene: KCNC3 were set to Spinocerebellar ataxia 13, MIM# 605259
Review for gene: KCNC3 was set to GREEN
Added comment: ID and ataxia, variable age of onset, including in childhood. Reported in ataxic CP cohort.
Sources: Expert list
Cerebral Palsy v0.150 ITPR1 Zornitza Stark Marked gene: ITPR1 as ready
Cerebral Palsy v0.150 ITPR1 Zornitza Stark Gene: itpr1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.150 ITPR1 Zornitza Stark Classified gene: ITPR1 as Green List (high evidence)
Cerebral Palsy v0.150 ITPR1 Zornitza Stark Gene: itpr1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.149 ITPR1 Zornitza Stark gene: ITPR1 was added
gene: ITPR1 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: ITPR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ITPR1 were set to 28826917; 25981959; 22986007
Phenotypes for gene: ITPR1 were set to Spinocerebellar ataxia 29, congenital nonprogressive MIM#117360
Review for gene: ITPR1 was set to GREEN
Added comment: Variants in this gene reported in individuals diagnosed with ataxic CP.
Sources: Expert list
Cerebral Palsy v0.148 IQSEC2 Zornitza Stark Marked gene: IQSEC2 as ready
Cerebral Palsy v0.148 IQSEC2 Zornitza Stark Gene: iqsec2 has been classified as Red List (Low Evidence).
Cerebral Palsy v0.148 IQSEC2 Zornitza Stark gene: IQSEC2 was added
gene: IQSEC2 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: IQSEC2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: IQSEC2 were set to 33368194; 20473311; 23674175
Phenotypes for gene: IQSEC2 were set to Mental retardation, X-linked 1/78, MIM# 309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347
Review for gene: IQSEC2 was set to RED
Added comment: More than 20 unrelated families reported. Typical features are ID, microcephaly and hand stereotypies. Phenotypic overlap with Angelman-Rett-like syndromes rather than CP.
Sources: Expert list
Cerebral Palsy v0.147 HPCA Zornitza Stark Marked gene: HPCA as ready
Cerebral Palsy v0.147 HPCA Zornitza Stark Gene: hpca has been classified as Red List (Low Evidence).
Cerebral Palsy v0.147 HPCA Zornitza Stark changed review comment from: Isolated dystonia, variable age of onset, including in adolescence. Insufficient phenotypic overlap with CP.
Sources: Expert list; to: Four families reported. Isolated dystonia, variable age of onset, including in adolescence. Insufficient phenotypic overlap with CP.
Sources: Expert list
Cerebral Palsy v0.147 HPCA Zornitza Stark gene: HPCA was added
gene: HPCA was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: HPCA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HPCA were set to 30145809; 25799108
Phenotypes for gene: HPCA were set to Dystonia 2, torsion, autosomal recessive, MIM#224500
Review for gene: HPCA was set to RED
Added comment: Isolated dystonia, variable age of onset, including in adolescence. Insufficient phenotypic overlap with CP.
Sources: Expert list
Microcephaly v1.53 MINPP1 Zornitza Stark Phenotypes for gene: MINPP1 were changed from Pontocerebellar hypoplasia to Pontocerebellar hypoplasia, type 16, MIM# 619527
Microcephaly v1.52 MINPP1 Zornitza Stark edited their review of gene: MINPP1: Changed phenotypes: Pontocerebellar hypoplasia, type 16, MIM# 619527
Mendeliome v0.9236 MINPP1 Zornitza Stark Phenotypes for gene: MINPP1 were changed from Pontocerebellar hypoplasia to Pontocerebellar hypoplasia, type 16, MIM# 619527
Mendeliome v0.9235 MINPP1 Zornitza Stark edited their review of gene: MINPP1: Changed phenotypes: Pontocerebellar hypoplasia, type 16, MIM# 619527
Cerebral Palsy v0.146 MINPP1 Zornitza Stark Phenotypes for gene: MINPP1 were changed from Pontocerebellar hypoplasia to Pontocerebellar hypoplasia, type 16, MIM# 619527
Cerebral Palsy v0.145 MINPP1 Zornitza Stark edited their review of gene: MINPP1: Changed phenotypes: Pontocerebellar hypoplasia, type 16, MIM# 619527
Cerebellar and Pontocerebellar Hypoplasia v1.17 MINPP1 Zornitza Stark Phenotypes for gene: MINPP1 were changed from Pontocerebellar hypoplasia to Pontocerebellar hypoplasia, type 16, MIM# 619527
Cerebellar and Pontocerebellar Hypoplasia v1.16 MINPP1 Zornitza Stark edited their review of gene: MINPP1: Changed phenotypes: Pontocerebellar hypoplasia, type 16, MIM# 619527
Arthrogryposis v0.298 ZC4H2 Zornitza Stark Publications for gene: ZC4H2 were set to 23623388; 31885220
Arthrogryposis v0.297 ZC4H2 Zornitza Stark Mode of inheritance for gene: ZC4H2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Arthrogryposis v0.296 ZC4H2 Zornitza Stark reviewed gene: ZC4H2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23623388, 34322088, 33949289, 31885220, 31206972; Phenotypes: Wieacker-Wolff syndrome, MIM# 314580; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.9235 ZC4H2 Zornitza Stark Marked gene: ZC4H2 as ready
Mendeliome v0.9235 ZC4H2 Zornitza Stark Gene: zc4h2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4136 ZC4H2 Zornitza Stark Marked gene: ZC4H2 as ready
Intellectual disability syndromic and non-syndromic v0.4136 ZC4H2 Zornitza Stark Gene: zc4h2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4136 ZC4H2 Zornitza Stark Phenotypes for gene: ZC4H2 were changed from to Wieacker-Wolff syndrome, MIM# 314580
Intellectual disability syndromic and non-syndromic v0.4135 ZC4H2 Zornitza Stark Publications for gene: ZC4H2 were set to
Intellectual disability syndromic and non-syndromic v0.4134 ZC4H2 Zornitza Stark Mode of inheritance for gene: ZC4H2 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.4133 ZC4H2 Zornitza Stark reviewed gene: ZC4H2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23623388, 34322088, 33949289, 31885220, 31206972; Phenotypes: Wieacker-Wolff syndrome, MIM# 314580; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.9235 ZC4H2 Zornitza Stark Phenotypes for gene: ZC4H2 were changed from to Wieacker-Wolff syndrome, MIM# 314580
Mendeliome v0.9234 ZC4H2 Zornitza Stark Publications for gene: ZC4H2 were set to
Mendeliome v0.9233 ZC4H2 Zornitza Stark Mode of inheritance for gene: ZC4H2 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v0.145 ZC4H2 Zornitza Stark Publications for gene: ZC4H2 were set to 23623388
Cerebral Palsy v0.144 ZC4H2 Zornitza Stark changed review comment from: Intellectual disability and spasticity are key features. At least one family had a diagnosis of CP.; to: Intellectual disability and spasticity are key features, more than 40 families reported. At least one family had a diagnosis of CP.
Cerebral Palsy v0.144 ZC4H2 Zornitza Stark edited their review of gene: ZC4H2: Changed publications: 23623388, 34322088, 33949289, 31885220, 31206972
Mendeliome v0.9232 ZC4H2 Zornitza Stark reviewed gene: ZC4H2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23623388, 34322088, 33949289, 31885220, 31206972; Phenotypes: Wieacker-Wolff syndrome, MIM# 314580; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v0.144 ZC4H2 Zornitza Stark Marked gene: ZC4H2 as ready
Cerebral Palsy v0.144 ZC4H2 Zornitza Stark Gene: zc4h2 has been classified as Green List (High Evidence).
Cerebral Palsy v0.144 ZC4H2 Zornitza Stark Phenotypes for gene: ZC4H2 were changed from to Wieacker-Wolff syndrome, MIM# 314580
Cerebral Palsy v0.143 ZC4H2 Zornitza Stark Publications for gene: ZC4H2 were set to
Cerebral Palsy v0.142 ZC4H2 Zornitza Stark Mode of inheritance for gene: ZC4H2 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v0.141 ZC4H2 Zornitza Stark reviewed gene: ZC4H2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23623388; Phenotypes: Wieacker-Wolff syndrome, MIM# 314580; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v0.141 SPG11 Zornitza Stark Marked gene: SPG11 as ready
Cerebral Palsy v0.141 SPG11 Zornitza Stark Gene: spg11 has been classified as Green List (High Evidence).
Cerebral Palsy v0.141 SPG11 Zornitza Stark Classified gene: SPG11 as Green List (high evidence)
Cerebral Palsy v0.141 SPG11 Zornitza Stark Gene: spg11 has been classified as Green List (High Evidence).
Cerebral Palsy v0.140 SPG11 Zornitza Stark gene: SPG11 was added
gene: SPG11 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: SPG11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPG11 were set to 34183250; 33581793
Phenotypes for gene: SPG11 were set to Spastic paraplegia 11, autosomal recessive, MIM# 604360
Review for gene: SPG11 was set to GREEN
Added comment: Intellectual disability and spasticity, reported in CP cohort.

Recent review of >300 individuals with SPG11-related disease. Mean age at onset was 13.10 ± 3.65 years, with initial symptoms like gait disturbance (107/195, 54.87%) and intellectual disability (47/195, 24.10%). Cognitive decline (228/270, 84.44%) was the most common complex manifestation stepped by dysarthria (134/195, 68.72%), neuropathy (112/177, 63.28%), amyatrophy, sphincter disturbance (60/130, 46.15%) and ataxia (90/194, 46.39%).
Sources: Expert list
Cerebral Palsy v0.139 SMARCB1 Zornitza Stark Marked gene: SMARCB1 as ready
Cerebral Palsy v0.139 SMARCB1 Zornitza Stark Gene: smarcb1 has been classified as Red List (Low Evidence).
Cerebral Palsy v0.139 SMARCB1 Zornitza Stark gene: SMARCB1 was added
gene: SMARCB1 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: SMARCB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SMARCB1 were set to Coffin-Siris syndrome 3, MIM# 614608
Review for gene: SMARCB1 was set to RED
Added comment: Intellectual disability and dysmorphic features, no strong phenotypic overlap with CP.
Sources: Expert list
Genetic Epilepsy v0.1226 ACOX1 Zornitza Stark Marked gene: ACOX1 as ready
Genetic Epilepsy v0.1226 ACOX1 Zornitza Stark Gene: acox1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1226 ACOX1 Zornitza Stark Phenotypes for gene: ACOX1 were changed from to Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470; Mitchell syndrome, MIM# 618960
Genetic Epilepsy v0.1225 ACOX1 Zornitza Stark Publications for gene: ACOX1 were set to
Genetic Epilepsy v0.1224 ACOX1 Zornitza Stark Mode of inheritance for gene: ACOX1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.1223 ACOX1 Zornitza Stark reviewed gene: ACOX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32169171, 17458872; Phenotypes: Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470, Mitchell syndrome, MIM# 618960; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.1223 ALX4 Zornitza Stark Marked gene: ALX4 as ready
Genetic Epilepsy v0.1223 ALX4 Zornitza Stark Gene: alx4 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1223 ALX4 Zornitza Stark gene: ALX4 was added
gene: ALX4 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: ALX4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALX4 were set to 33269135
Phenotypes for gene: ALX4 were set to Parietal foramina 2, MIM# 609597
Review for gene: ALX4 was set to RED
Added comment: Single case report of seizures in an individual with ALX4 variant and parietal foramina, unclear if related.
Sources: Expert Review
Genetic Epilepsy v0.1222 ADGRV1 Zornitza Stark Phenotypes for gene: ADGRV1 were changed from Myoclonic epilepsy; febrile seizures; epilepsy to Myoclonic epilepsy; febrile seizures; epilepsy; Rolandic epilepsy
Genetic Epilepsy v0.1221 ADGRV1 Zornitza Stark Publications for gene: ADGRV1 were set to 29266188; 29261713; 32962041
Genetic Epilepsy v0.1220 ADGRV1 Zornitza Stark Mode of inheritance for gene: ADGRV1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.1219 ADGRV1 Zornitza Stark Classified gene: ADGRV1 as Amber List (moderate evidence)
Genetic Epilepsy v0.1219 ADGRV1 Zornitza Stark Gene: adgrv1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1218 ADGRV1 Zornitza Stark edited their review of gene: ADGRV1: Added comment: Two families reported with bi-allelic variants and Rolandic epilepsy.; Changed rating: AMBER; Changed publications: 29266188, 29261713, 32962041, 34160719; Changed phenotypes: Myoclonic epilepsy, febrile seizures, epilepsy, Rolandic epilepsy; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.1218 ACTG1 Zornitza Stark Classified gene: ACTG1 as Green List (high evidence)
Genetic Epilepsy v0.1218 ACTG1 Zornitza Stark Gene: actg1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1218 ACTG1 Zornitza Stark Classified gene: ACTG1 as Green List (high evidence)
Genetic Epilepsy v0.1218 ACTG1 Zornitza Stark Gene: actg1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1218 ACTG1 Zornitza Stark Marked gene: ACTG1 as ready
Genetic Epilepsy v0.1218 ACTG1 Zornitza Stark Gene: actg1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1218 ACTG1 Zornitza Stark Classified gene: ACTG1 as Green List (high evidence)
Genetic Epilepsy v0.1218 ACTG1 Zornitza Stark Gene: actg1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1217 ACTG1 Zornitza Stark gene: ACTG1 was added
gene: ACTG1 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: ACTG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ACTG1 were set to 22366783; 25052316
Phenotypes for gene: ACTG1 were set to Baraitser-Winter syndrome 2, MIM# 614583
Review for gene: ACTG1 was set to GREEN
Added comment: Well established gene-disease association. ID and seizures correlate with extent of brain anomalies.
Sources: Expert Review
Genetic Epilepsy v0.1216 AARS2 Zornitza Stark Publications for gene: AARS2 were set to 21549344; 25817015
Genetic Epilepsy v0.1215 AARS2 Zornitza Stark Classified gene: AARS2 as Amber List (moderate evidence)
Genetic Epilepsy v0.1215 AARS2 Zornitza Stark Gene: aars2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1214 AARS2 Zornitza Stark changed review comment from: Seizures not a prominent feature of these conditions.; to: Seizures reported in some.
Genetic Epilepsy v0.1214 AARS2 Zornitza Stark edited their review of gene: AARS2: Changed rating: AMBER; Changed publications: 21549344, 25817015, 32571458, 24808023
Genetic Epilepsy v0.1214 TUBB3 Zornitza Stark Marked gene: TUBB3 as ready
Genetic Epilepsy v0.1214 TUBB3 Zornitza Stark Gene: tubb3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1214 TUBB3 Zornitza Stark Phenotypes for gene: TUBB3 were changed from to Cortical dysplasia, complex, with other brain malformations 1, MIM# 614039
Genetic Epilepsy v0.1213 TUBB3 Zornitza Stark Publications for gene: TUBB3 were set to
Genetic Epilepsy v0.1212 TUBB3 Zornitza Stark Mode of inheritance for gene: TUBB3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1211 TUBB3 Zornitza Stark reviewed gene: TUBB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 20829227, 25059107, 33318778; Phenotypes: Cortical dysplasia, complex, with other brain malformations 1, MIM# 614039; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1211 SLC4A4 Zornitza Stark Marked gene: SLC4A4 as ready
Genetic Epilepsy v0.1211 SLC4A4 Zornitza Stark Gene: slc4a4 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1211 SLC4A4 Zornitza Stark gene: SLC4A4 was added
gene: SLC4A4 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: SLC4A4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC4A4 were set to 33439394
Phenotypes for gene: SLC4A4 were set to Renal tubular acidosis, proximal, with ocular abnormalities, MIM# 604278
Review for gene: SLC4A4 was set to RED
Added comment: Bi-allelic variants in SLC4A4 cause a syndrome characterised by proximal renal tubular acidosis (pRTA), ID, dental and ocular abnormalities, and hemiplegic migraine.

Single family reported with 4 affected individuals, where seizures were a prominent feature, with adult onset. Two developed life-threatening status epilepticus.
Sources: Expert Review
Regression v0.375 SLC1A3 Zornitza Stark Marked gene: SLC1A3 as ready
Regression v0.375 SLC1A3 Zornitza Stark Gene: slc1a3 has been classified as Red List (Low Evidence).
Regression v0.375 SLC1A3 Zornitza Stark Phenotypes for gene: SLC1A3 were changed from to Episodic ataxia, type 6, MIM# 612656
Regression v0.374 SLC1A3 Zornitza Stark Publications for gene: SLC1A3 were set to
Regression v0.373 SLC1A3 Zornitza Stark Mode of inheritance for gene: SLC1A3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1210 SLC1A3 Zornitza Stark Marked gene: SLC1A3 as ready
Genetic Epilepsy v0.1210 SLC1A3 Zornitza Stark Gene: slc1a3 has been classified as Green List (High Evidence).
Regression v0.372 SLC1A3 Zornitza Stark Classified gene: SLC1A3 as Red List (low evidence)
Regression v0.372 SLC1A3 Zornitza Stark Gene: slc1a3 has been classified as Red List (Low Evidence).
Regression v0.371 SLC1A3 Zornitza Stark reviewed gene: SLC1A3: Rating: RED; Mode of pathogenicity: None; Publications: 19139306, 16116111, 29208948, 27829685, 32741053; Phenotypes: Episodic ataxia, type 6, MIM# 612656; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1210 SLC1A3 Zornitza Stark Classified gene: SLC1A3 as Green List (high evidence)
Genetic Epilepsy v0.1210 SLC1A3 Zornitza Stark Gene: slc1a3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1209 SLC1A3 Zornitza Stark gene: SLC1A3 was added
gene: SLC1A3 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: SLC1A3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC1A3 were set to 19139306; 16116111; 29208948; 27829685; 32741053
Phenotypes for gene: SLC1A3 were set to Episodic ataxia, type 6, MIM# 612656
Review for gene: SLC1A3 was set to GREEN
Added comment: Seven families reported. Episodic ataxia type 6 (EA6) differs from other EA forms in long attack duration, epilepsy and absent myokymia, nystagmus, and tinnitus.
Sources: Expert Review
Genetic Epilepsy v0.1208 MAST1 Zornitza Stark Marked gene: MAST1 as ready
Genetic Epilepsy v0.1208 MAST1 Zornitza Stark Gene: mast1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1208 MAST1 Zornitza Stark Classified gene: MAST1 as Green List (high evidence)
Genetic Epilepsy v0.1208 MAST1 Zornitza Stark Gene: mast1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1207 MAST1 Zornitza Stark gene: MAST1 was added
gene: MAST1 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: MAST1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAST1 were set to 31721002; 30449657; 32198973
Phenotypes for gene: MAST1 were set to Mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations; OMIM #618273
Review for gene: MAST1 was set to GREEN
Added comment: 7 unrelated patients with mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations (MCCCHCM) with de novo heterozygous mutations in MAST1 gene. Intellectual disability and seizures are clinical features, together with characteristic brain imaging abnormalities.

In vitro functional studies showed that 1 of the variants (lys276del) increased MAST1 binding to microtubules compared to controls. Mutant mice heterozygous for a Mast1 leu278del allele showed a thicker corpus callosum compared to wildtype, and an overall reduction in cortical volume and thickness and decreased cerebellar volume and number of granule and Purkinje cells due to increased apoptosis compared to controls.

1 Emirati patient with ID, microcephaly, and dysmorphic features, with missense variant in MAST1.
Sources: Expert Review
Genetic Epilepsy v0.1206 LAMA2 Zornitza Stark Classified gene: LAMA2 as Green List (high evidence)
Genetic Epilepsy v0.1206 LAMA2 Zornitza Stark Gene: lama2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1205 LAMA2 Zornitza Stark Classified gene: LAMA2 as Green List (high evidence)
Genetic Epilepsy v0.1205 LAMA2 Zornitza Stark Gene: lama2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1204 LAMA2 Zornitza Stark Marked gene: LAMA2 as ready
Genetic Epilepsy v0.1204 LAMA2 Zornitza Stark Gene: lama2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1204 LAMA2 Zornitza Stark gene: LAMA2 was added
gene: LAMA2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: LAMA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LAMA2 were set to 33333793; 34325301
Phenotypes for gene: LAMA2 were set to Muscular dystrophy, congenital, merosin deficient or partially deficient, MIM# 607855; Muscular dystrophy, limb-girdle, autosomal recessive 23 , MIM#618138
Review for gene: LAMA2 was set to GREEN
Added comment: Epilepsy is a common, often severe, feature of LAMA2-related muscular dystrophy (LAMA2-RD) and could represent its onset and main manifestation, even in the absence of overt muscle involvement, reviewed in PMID 34325301.
Sources: Literature
Genetic Epilepsy v0.1203 CIC Zornitza Stark Marked gene: CIC as ready
Genetic Epilepsy v0.1203 CIC Zornitza Stark Gene: cic has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1203 CIC Zornitza Stark Phenotypes for gene: CIC were changed from to Mental retardation, autosomal dominant 45, MIM# 617600
Genetic Epilepsy v0.1202 CIC Zornitza Stark Publications for gene: CIC were set to
Genetic Epilepsy v0.1201 CIC Zornitza Stark Mode of inheritance for gene: CIC was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1200 CIC Zornitza Stark reviewed gene: CIC: Rating: GREEN; Mode of pathogenicity: None; Publications: 28288114; Phenotypes: Mental retardation, autosomal dominant 45, MIM# 617600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1200 BRAF Zornitza Stark Marked gene: BRAF as ready
Genetic Epilepsy v0.1200 BRAF Zornitza Stark Gene: braf has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1200 BRAF Zornitza Stark Phenotypes for gene: BRAF were changed from to Cardiofaciocutaneous syndrome, MIM# 115150
Genetic Epilepsy v0.1199 BRAF Zornitza Stark Publications for gene: BRAF were set to
Genetic Epilepsy v0.1198 BRAF Zornitza Stark Mode of inheritance for gene: BRAF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1197 BRAF Zornitza Stark reviewed gene: BRAF: Rating: GREEN; Mode of pathogenicity: None; Publications: 34309696; Phenotypes: Cardiofaciocutaneous syndrome, MIM# 115150; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Disorders of Glycosylation v1.19 ALG10 Zornitza Stark Marked gene: ALG10 as ready
Congenital Disorders of Glycosylation v1.19 ALG10 Zornitza Stark Gene: alg10 has been classified as Red List (Low Evidence).
Congenital Disorders of Glycosylation v1.19 ALG10 Zornitza Stark gene: ALG10 was added
gene: ALG10 was added to Congenital Disorders of Glycosylation. Sources: Literature
Mode of inheritance for gene: ALG10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALG10 were set to 33798445
Phenotypes for gene: ALG10 were set to Progressive myoclonus epilepsy; CDG
Review for gene: ALG10 was set to RED
Added comment: Single individual with homozygous variant identified in a progressive myoclonus epilepsy cohort.
Sources: Literature
Genetic Epilepsy v0.1197 ALG10 Zornitza Stark Marked gene: ALG10 as ready
Genetic Epilepsy v0.1197 ALG10 Zornitza Stark Gene: alg10 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1197 ALG10 Zornitza Stark gene: ALG10 was added
gene: ALG10 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ALG10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALG10 were set to 33798445
Phenotypes for gene: ALG10 were set to Progressive myoclonus epilepsy; CDG
Review for gene: ALG10 was set to RED
Added comment: Single individual with homozygous variant identified in a progressive myoclonus epilepsy cohort.
Sources: Literature
Mendeliome v0.9232 ALG10 Zornitza Stark Marked gene: ALG10 as ready
Mendeliome v0.9232 ALG10 Zornitza Stark Gene: alg10 has been classified as Red List (Low Evidence).
Mendeliome v0.9232 ALG10 Zornitza Stark gene: ALG10 was added
gene: ALG10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ALG10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALG10 were set to 33798445
Phenotypes for gene: ALG10 were set to Progressive myoclonus epilepsy; CDG
Review for gene: ALG10 was set to RED
Added comment: Single individual with homozygous variant identified in a progressive myoclonus epilepsy cohort.
Sources: Literature
Mendeliome v0.9231 LRRK1 Zornitza Stark Marked gene: LRRK1 as ready
Mendeliome v0.9231 LRRK1 Zornitza Stark Gene: lrrk1 has been classified as Green List (High Evidence).
Mendeliome v0.9231 LRRK1 Zornitza Stark Classified gene: LRRK1 as Green List (high evidence)
Mendeliome v0.9231 LRRK1 Zornitza Stark Gene: lrrk1 has been classified as Green List (High Evidence).
Mendeliome v0.9230 LRRK1 Zornitza Stark gene: LRRK1 was added
gene: LRRK1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: LRRK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRRK1 were set to 27829680; 27055475; 31571209; 32119750
Phenotypes for gene: LRRK1 were set to Osteosclerotic metaphyseal dysplasia (OSMD) (OMIM: 615198)
Review for gene: LRRK1 was set to GREEN
Added comment: At least 4 unrelated families reported.
Sources: Expert Review
Skeletal dysplasia v0.123 LRRK1 Zornitza Stark Marked gene: LRRK1 as ready
Skeletal dysplasia v0.123 LRRK1 Zornitza Stark Gene: lrrk1 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.123 LRRK1 Zornitza Stark Classified gene: LRRK1 as Green List (high evidence)
Skeletal dysplasia v0.123 LRRK1 Zornitza Stark Gene: lrrk1 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.122 LRRK1 Zornitza Stark gene: LRRK1 was added
gene: LRRK1 was added to Skeletal dysplasia. Sources: Expert Review
Mode of inheritance for gene: LRRK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRRK1 were set to 27829680; 27055475; 31571209; 32119750
Phenotypes for gene: LRRK1 were set to Osteosclerotic metaphyseal dysplasia (OSMD) (OMIM: 615198)
Review for gene: LRRK1 was set to GREEN
Added comment: At least 4 unrelated families reported.
Sources: Expert Review
Genetic Epilepsy v0.1196 KIF4A Zornitza Stark gene: KIF4A was added
gene: KIF4A was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: KIF4A was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: KIF4A were set to 24812067; 34346154
Phenotypes for gene: KIF4A were set to Mental retardation, X-linked 100, MIM# 300923
Review for gene: KIF4A was set to AMBER
Added comment: 12 families reported. Major structural brain abnormalities present in at least 3 (hydrocephalus), variable ID in several. At least 3 reported as having seizures, though variable severity (including febrile Sz in one).
Sources: Expert Review
Hydrocephalus_Ventriculomegaly v0.96 KIF4A Zornitza Stark Marked gene: KIF4A as ready
Hydrocephalus_Ventriculomegaly v0.96 KIF4A Zornitza Stark Gene: kif4a has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.96 KIF4A Zornitza Stark Classified gene: KIF4A as Green List (high evidence)
Hydrocephalus_Ventriculomegaly v0.96 KIF4A Zornitza Stark Gene: kif4a has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.95 KIF4A Zornitza Stark gene: KIF4A was added
gene: KIF4A was added to Hydrocephalus_Ventriculomegaly. Sources: Expert Review
Mode of inheritance for gene: KIF4A was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: KIF4A were set to 24812067; 34346154; 30679815
Phenotypes for gene: KIF4A were set to Mental retardation, X-linked 100, MIM# 300923
Review for gene: KIF4A was set to GREEN
Added comment: 12 families reported. Severe hydrocephalus present in at least 3.
Sources: Expert Review
Mendeliome v0.9229 KIF4A Zornitza Stark Publications for gene: KIF4A were set to 24812067
Mendeliome v0.9228 KIF4A Zornitza Stark Classified gene: KIF4A as Green List (high evidence)
Mendeliome v0.9228 KIF4A Zornitza Stark Gene: kif4a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4133 KIF4A Zornitza Stark Publications for gene: KIF4A were set to 24812067; 34346154
Intellectual disability syndromic and non-syndromic v0.4133 KIF4A Zornitza Stark Publications for gene: KIF4A were set to 24812067
Mendeliome v0.9227 KIF4A Zornitza Stark edited their review of gene: KIF4A: Added comment: Further 11 families reported. Major structural brain abnormalities present in at least 3 (hydrocephalus), variable ID in several.; Changed rating: GREEN; Changed publications: 24812067, 34346154
Intellectual disability syndromic and non-syndromic v0.4132 KIF4A Zornitza Stark Classified gene: KIF4A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4132 KIF4A Zornitza Stark Gene: kif4a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4131 KIF4A Zornitza Stark edited their review of gene: KIF4A: Added comment: Further 11 families reported. Major structural brain abnormalities present in at least 3 (hydrocephalus), variable ID in several.; Changed rating: GREEN; Changed publications: 24812067, 34346154
Mendeliome v0.9227 HNRNPH1 Zornitza Stark Marked gene: HNRNPH1 as ready
Mendeliome v0.9227 HNRNPH1 Zornitza Stark Gene: hnrnph1 has been classified as Green List (High Evidence).
Mendeliome v0.9227 HNRNPH1 Zornitza Stark Classified gene: HNRNPH1 as Green List (high evidence)
Mendeliome v0.9227 HNRNPH1 Zornitza Stark Gene: hnrnph1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.138 PAK3 Zornitza Stark Marked gene: PAK3 as ready
Cerebral Palsy v0.138 PAK3 Zornitza Stark Gene: pak3 has been classified as Red List (Low Evidence).
Cerebral Palsy v0.138 PAK3 Zornitza Stark Phenotypes for gene: PAK3 were changed from to Intellectual developmental disorder, X-linked 30, MIM# 300558
Cerebral Palsy v0.137 PAK3 Zornitza Stark Publications for gene: PAK3 were set to
Cerebral Palsy v0.136 PAK3 Zornitza Stark Mode of inheritance for gene: PAK3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebral Palsy v0.135 PAK3 Zornitza Stark Classified gene: PAK3 as Red List (low evidence)
Cerebral Palsy v0.135 PAK3 Zornitza Stark Gene: pak3 has been classified as Red List (Low Evidence).
Cerebral Palsy v0.134 PAK3 Zornitza Stark reviewed gene: PAK3: Rating: RED; Mode of pathogenicity: None; Publications: 25666757; Phenotypes: Intellectual developmental disorder, X-linked 30, MIM# 300558; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebral Palsy v0.134 SLC2A1 Zornitza Stark Marked gene: SLC2A1 as ready
Cerebral Palsy v0.134 SLC2A1 Zornitza Stark Gene: slc2a1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.134 SLC2A1 Zornitza Stark Classified gene: SLC2A1 as Green List (high evidence)
Cerebral Palsy v0.134 SLC2A1 Zornitza Stark Gene: slc2a1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.133 SLC2A1 Zornitza Stark gene: SLC2A1 was added
gene: SLC2A1 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: SLC2A1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SLC2A1 were set to 30799092; 18451999; 20129935; 10980529; 20221955; 31196579
Phenotypes for gene: SLC2A1 were set to GLUT1 deficiency syndrome 1, infantile onset, severe, 606777; GLUT1 deficiency syndrome 2, childhood onset, 612126; Disorders of glucose transport
Review for gene: SLC2A1 was set to GREEN
Added comment: Well established gene-disease association. Mixture of ID and movement disorders, reported in a CP cohort. Treatable.
Sources: Expert list
Mendeliome v0.9226 IRGM Zornitza Stark Marked gene: IRGM as ready
Mendeliome v0.9226 IRGM Zornitza Stark Gene: irgm has been classified as Red List (Low Evidence).
Mendeliome v0.9226 IRGM Zornitza Stark Phenotypes for gene: IRGM were changed from to {Inflammatory bowel disease (Crohn disease) 19} MIM#612278
Mendeliome v0.9225 IRGM Zornitza Stark Publications for gene: IRGM were set to
Mendeliome v0.9224 IRGM Zornitza Stark Classified gene: IRGM as Red List (low evidence)
Mendeliome v0.9224 IRGM Zornitza Stark Gene: irgm has been classified as Red List (Low Evidence).
Mendeliome v0.9223 UTP4 Zornitza Stark Marked gene: UTP4 as ready
Mendeliome v0.9223 UTP4 Zornitza Stark Gene: utp4 has been classified as Red List (Low Evidence).
Mendeliome v0.9223 UTP4 Zornitza Stark Phenotypes for gene: UTP4 were changed from to North American Indian childhood cirrhosis
Mendeliome v0.9222 UTP4 Zornitza Stark Publications for gene: UTP4 were set to
Mendeliome v0.9221 UTP4 Zornitza Stark Mode of inheritance for gene: UTP4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9220 UTP4 Zornitza Stark Classified gene: UTP4 as Red List (low evidence)
Mendeliome v0.9220 UTP4 Zornitza Stark Gene: utp4 has been classified as Red List (Low Evidence).
Mendeliome v0.9219 UTP4 Zornitza Stark Tag refuted tag was added to gene: UTP4.
Mendeliome v0.9219 UTP4 Zornitza Stark reviewed gene: UTP4: Rating: RED; Mode of pathogenicity: None; Publications: 12417987, 27535533; Phenotypes: North American Indian childhood cirrhosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4131 FAM149B1 Zornitza Stark Marked gene: FAM149B1 as ready
Intellectual disability syndromic and non-syndromic v0.4131 FAM149B1 Zornitza Stark Gene: fam149b1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4131 FAM149B1 Zornitza Stark Classified gene: FAM149B1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4131 FAM149B1 Zornitza Stark Gene: fam149b1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.132 SCN1A Zornitza Stark Marked gene: SCN1A as ready
Cerebral Palsy v0.132 SCN1A Zornitza Stark Gene: scn1a has been classified as Green List (High Evidence).
Cerebral Palsy v0.132 SCN1A Zornitza Stark Classified gene: SCN1A as Green List (high evidence)
Cerebral Palsy v0.132 SCN1A Zornitza Stark Gene: scn1a has been classified as Green List (High Evidence).
Cerebral Palsy v0.131 PURA Zornitza Stark Marked gene: PURA as ready
Cerebral Palsy v0.131 PURA Zornitza Stark Gene: pura has been classified as Green List (High Evidence).
Cerebral Palsy v0.131 PURA Zornitza Stark Classified gene: PURA as Green List (high evidence)
Cerebral Palsy v0.131 PURA Zornitza Stark Gene: pura has been classified as Green List (High Evidence).
Cerebral Palsy v0.130 HECW2 Zornitza Stark Marked gene: HECW2 as ready
Cerebral Palsy v0.130 HECW2 Zornitza Stark Gene: hecw2 has been classified as Green List (High Evidence).
Mendeliome v0.9219 IRGM Paul De Fazio reviewed gene: IRGM: Rating: RED; Mode of pathogenicity: None; Publications: 17554261, 19299395, 18985712, 20106866, 21278745, 20360734; Phenotypes: {Inflammatory bowel disease (Crohn disease) 19} MIM#612278; Mode of inheritance: Unknown; Current diagnostic: yes
Cerebral Palsy v0.130 HECW2 Zornitza Stark Classified gene: HECW2 as Green List (high evidence)
Cerebral Palsy v0.130 HECW2 Zornitza Stark Gene: hecw2 has been classified as Green List (High Evidence).
Mendeliome v0.9219 UTP4 Michelle Torres reviewed gene: UTP4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.4130 FAM149B1 Michelle Torres gene: FAM149B1 was added
gene: FAM149B1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: FAM149B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM149B1 were set to 30905400
Phenotypes for gene: FAM149B1 were set to Joubert; Ciliopathy
Review for gene: FAM149B1 was set to GREEN
gene: FAM149B1 was marked as current diagnostic
Added comment: Four unrelated, but consanguineous, families reported with 2 truncating variants. Developmental delay with hypotonia and intellectual disability are typical features, and many children have characteristic facies.
Sources: Literature
Cerebral Palsy v0.129 SCN1A Clare van Eyk gene: SCN1A was added
gene: SCN1A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SCN1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCN1A were set to PMID: 33528536; PMID: 34364746; PMID: 34114234
Phenotypes for gene: SCN1A were set to Developmental and epileptic encephalopathy 6B, non-Dravet (OMIM 619317); Dravet syndrome (OMIM 607208)
Review for gene: SCN1A was set to GREEN
Added comment: Six cases described with missense (3 cases) or loss of function (3 cases) variants in SCN1A in individuals diagnosed with cerebral palsy. Mutations in SCN1A cause a spectrum of early-onset epileptic encephalopathies, with some cases reported to have movement disorders clinically overlapping with cerebral palsy.
Sources: Literature
Cerebral Palsy v0.129 PURA Clare van Eyk gene: PURA was added
gene: PURA was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PURA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PURA were set to PMID: 34077496
Phenotypes for gene: PURA were set to Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158)
Review for gene: PURA was set to GREEN
Added comment: PURA loss of function and missense variants cause a clinically variable neurodevelopmental disorder with movement disorders including dystonia and limb spasticity described in some individuals. One case with a novel frameshift deletion described with dyskinetic cerebral palsy and intellectual disability. An additional 3 cases with de novo variants (1 nonsense, 2 missense) reported in a retrospective analysis of a Clinical Laboratory referral cohort with cerebral palsy.
Sources: Literature
Cerebral Palsy v0.129 HECW2 Danielle Ariti gene: HECW2 was added
gene: HECW2 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: HECW2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HECW2 were set to 33528536; 33098801
Phenotypes for gene: HECW2 were set to Cerebral Palsy; Neurodevelopmental disorder with hypotonia, seizures, and absent language MIM# 617268
Review for gene: HECW2 was set to GREEN
Added comment: 3 individuals in CP cohort with mono-allelic (2x de novo & 1 unknown inheritance) HECW2 variants. All individuals were diagnosed with idiopathic dystonic CP.

HECW2 variants cause a neurodevelopmental disorder NDHSAL that presents with severe developmental delay, absent speech, epilepsy, encephalopathy, hypotonia, dystonia/dyskinesia, and macrocephaly.
Sources: Expert list
Repeat Disorders v0.148 FRA7A Bryony Thompson Classified STR: FRA7A as Amber List (moderate evidence)
Repeat Disorders v0.148 FRA7A Bryony Thompson Str: fra7a has been classified as Amber List (Moderate Evidence).
Limb and Digital Malformations SuperPanel v0.2 Bryony Thompson Changed child panels to: Radial Ray Abnormalities; Polydactyly; Hand and foot malformations
Cerebral Palsy v0.129 SHANK3 Zornitza Stark Marked gene: SHANK3 as ready
Cerebral Palsy v0.129 SHANK3 Zornitza Stark Gene: shank3 has been classified as Red List (Low Evidence).
Cerebral Palsy v0.129 SHANK3 Zornitza Stark gene: SHANK3 was added
gene: SHANK3 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: SHANK3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SHANK3 were set to 17173049
Phenotypes for gene: SHANK3 were set to Phelan-McDermid syndrome, MIM# 606232
Review for gene: SHANK3 was set to RED
Added comment: Note deletions are common. ID with severe speech impairment/autistic features but movement disorders are not prominent, so limited overlap clinically with CP.
Sources: Expert list
Cerebral Palsy v0.128 PIGN Zornitza Stark Marked gene: PIGN as ready
Cerebral Palsy v0.128 PIGN Zornitza Stark Gene: pign has been classified as Green List (High Evidence).
Cerebral Palsy v0.128 PIGN Zornitza Stark Classified gene: PIGN as Green List (high evidence)
Cerebral Palsy v0.128 PIGN Zornitza Stark Gene: pign has been classified as Green List (High Evidence).
Cerebral Palsy v0.127 PCDH19 Zornitza Stark Marked gene: PCDH19 as ready
Cerebral Palsy v0.127 PCDH19 Zornitza Stark Gene: pcdh19 has been classified as Red List (Low Evidence).
Cerebral Palsy v0.127 PCDH19 Zornitza Stark Classified gene: PCDH19 as Red List (low evidence)
Cerebral Palsy v0.127 PCDH19 Zornitza Stark Gene: pcdh19 has been classified as Red List (Low Evidence).
Cerebral Palsy v0.126 PCDH12 Zornitza Stark Marked gene: PCDH12 as ready
Cerebral Palsy v0.126 PCDH12 Zornitza Stark Gene: pcdh12 has been classified as Green List (High Evidence).
Cerebral Palsy v0.126 PCDH12 Zornitza Stark Classified gene: PCDH12 as Green List (high evidence)
Cerebral Palsy v0.126 PCDH12 Zornitza Stark Gene: pcdh12 has been classified as Green List (High Evidence).
Cerebral Palsy v0.125 GRIN2B Zornitza Stark Marked gene: GRIN2B as ready
Cerebral Palsy v0.125 GRIN2B Zornitza Stark Gene: grin2b has been classified as Green List (High Evidence).
Cerebral Palsy v0.125 GRIN2B Zornitza Stark Classified gene: GRIN2B as Green List (high evidence)
Cerebral Palsy v0.125 GRIN2B Zornitza Stark Gene: grin2b has been classified as Green List (High Evidence).
Cerebral Palsy v0.124 GNAO1 Zornitza Stark Marked gene: GNAO1 as ready
Cerebral Palsy v0.124 GNAO1 Zornitza Stark Gene: gnao1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.124 GNAO1 Zornitza Stark Classified gene: GNAO1 as Green List (high evidence)
Cerebral Palsy v0.124 GNAO1 Zornitza Stark Gene: gnao1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.123 FOXG1 Zornitza Stark Marked gene: FOXG1 as ready
Cerebral Palsy v0.123 FOXG1 Zornitza Stark Gene: foxg1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.123 FOXG1 Zornitza Stark Classified gene: FOXG1 as Green List (high evidence)
Cerebral Palsy v0.123 FOXG1 Zornitza Stark Gene: foxg1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.122 GNB1 Zornitza Stark Marked gene: GNB1 as ready
Cerebral Palsy v0.122 GNB1 Zornitza Stark Gene: gnb1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.122 GNB1 Zornitza Stark Classified gene: GNB1 as Green List (high evidence)
Cerebral Palsy v0.122 GNB1 Zornitza Stark Gene: gnb1 has been classified as Green List (High Evidence).
Limb and Digital Malformations SuperPanel v0.0 Bryony Thompson Added Panel Limb and Digital Malformations SuperPanel
Set child panels to: Polydactyly; Hand and foot malformations
Set panel types to: Superpanel; Royal Melbourne Hospital; Rare Disease
Hand and foot malformations v0.55 Bryony Thompson Panel name changed from Hand and foot malformation to Hand and foot malformations
Panel status changed from internal to public
Hand and foot malformations v0.54 WNT3 Bryony Thompson Marked gene: WNT3 as ready
Hand and foot malformations v0.54 WNT3 Bryony Thompson Gene: wnt3 has been classified as Red List (Low Evidence).
Hand and foot malformations v0.54 WNT3 Bryony Thompson Publications for gene: WNT3 were set to
Hand and foot malformations v0.53 TGDS Bryony Thompson Marked gene: TGDS as ready
Hand and foot malformations v0.53 TGDS Bryony Thompson Gene: tgds has been classified as Green List (High Evidence).
Hand and foot malformations v0.53 TGDS Bryony Thompson Publications for gene: TGDS were set to
Hand and foot malformations v0.52 TGDS Bryony Thompson Classified gene: TGDS as Green List (high evidence)
Hand and foot malformations v0.52 TGDS Bryony Thompson Gene: tgds has been classified as Green List (High Evidence).
Hand and foot malformations v0.51 TGDS Bryony Thompson reviewed gene: TGDS: Rating: GREEN; Mode of pathogenicity: None; Publications: 25480037; Phenotypes: Catel-Manzke syndrome MIM#616145; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hand and foot malformations v0.51 SMARCE1 Bryony Thompson Marked gene: SMARCE1 as ready
Hand and foot malformations v0.51 SMARCE1 Bryony Thompson Gene: smarce1 has been classified as Green List (High Evidence).
Hand and foot malformations v0.51 SMARCE1 Bryony Thompson Publications for gene: SMARCE1 were set to
Hand and foot malformations v0.50 SMARCE1 Bryony Thompson Classified gene: SMARCE1 as Green List (high evidence)
Hand and foot malformations v0.50 SMARCE1 Bryony Thompson Gene: smarce1 has been classified as Green List (High Evidence).
Hand and foot malformations v0.49 SMARCE1 Bryony Thompson edited their review of gene: SMARCE1: Set current diagnostic: yes
Hand and foot malformations v0.49 SMARCE1 Bryony Thompson reviewed gene: SMARCE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22426308, 25169878, 34205270; Phenotypes: Coffin-Siris syndrome 5 MIM#616938; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v0.121 GRIN2B Danielle Ariti gene: GRIN2B was added
gene: GRIN2B was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: GRIN2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GRIN2B were set to 34531397; 33528536
Phenotypes for gene: GRIN2B were set to Cerebral Palsy; Developmental and epileptic encephalopathy 27 MIM# 616139; Intellectual developmental disorder, autosomal dominant 6, with or without seizures MIM# 613970
Review for gene: GRIN2B was set to GREEN
Added comment: 3 individuals in CP cohort with mono-allelic (2x de novo & 1 unknown inheritance) GRIN2B variants.

GRIN2B variants cause autosomal dominant neurodevelopmental disorders DEE27 and MRD6 that present with intellectual disability, seizures, hypotonia, movement disorders, and autistic features.
Sources: Expert list
Cerebral Palsy v0.121 GNB1 Danielle Ariti gene: GNB1 was added
gene: GNB1 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: GNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GNB1 were set to 33528536; 32989326; 34531397; 30194818
Phenotypes for gene: GNB1 were set to Cerebral Palsy; Mental retardation, autosomal dominant 42 MIM# 616973
Review for gene: GNB1 was set to GREEN
Added comment: 4 individuals in CP cohort reported with mono-allelic (3x de novo & 1x unknown inheritance) GNB1 variants. All individuals presented with impaired movement (dystonia, spasticity) and ID; additional features were growth delay, ADHD and seizures.

Additionally, all individuals had substitution affecting the p.Ile80 residue in exon 6 (28% of MRD42 cases carry variants at this residue and tend to present with Dystonia and growth delay more frequently than other residue-variant cases)
Sources: Expert list
Hand and foot malformations v0.49 SMARCB1 Bryony Thompson Marked gene: SMARCB1 as ready
Hand and foot malformations v0.49 SMARCB1 Bryony Thompson Gene: smarcb1 has been classified as Green List (High Evidence).
Hand and foot malformations v0.49 SMARCB1 Bryony Thompson Publications for gene: SMARCB1 were set to
Hand and foot malformations v0.48 SMARCB1 Bryony Thompson Classified gene: SMARCB1 as Green List (high evidence)
Hand and foot malformations v0.48 SMARCB1 Bryony Thompson Gene: smarcb1 has been classified as Green List (High Evidence).
Hand and foot malformations v0.47 SMARCB1 Bryony Thompson reviewed gene: SMARCB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22426308, 25169878; Phenotypes: Coffin-Siris syndrome 3 MIM#614608; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hand and foot malformations v0.47 SMARCA4 Bryony Thompson Marked gene: SMARCA4 as ready
Hand and foot malformations v0.47 SMARCA4 Bryony Thompson Gene: smarca4 has been classified as Green List (High Evidence).
Hand and foot malformations v0.47 SMARCA4 Bryony Thompson Publications for gene: SMARCA4 were set to
Hand and foot malformations v0.46 SMARCA4 Bryony Thompson Classified gene: SMARCA4 as Green List (high evidence)
Hand and foot malformations v0.46 SMARCA4 Bryony Thompson Gene: smarca4 has been classified as Green List (High Evidence).
Hand and foot malformations v0.45 SMARCA4 Bryony Thompson reviewed gene: SMARCA4: Rating: GREEN; Mode of pathogenicity: None; Publications: 22426308; Phenotypes: Coffin-Siris syndrome 4 MIM#614609; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hand and foot malformations v0.45 SMARCA2 Bryony Thompson Marked gene: SMARCA2 as ready
Hand and foot malformations v0.45 SMARCA2 Bryony Thompson Gene: smarca2 has been classified as Green List (High Evidence).
Hand and foot malformations v0.45 SMARCA2 Bryony Thompson Mode of pathogenicity for gene: SMARCA2 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Hand and foot malformations v0.44 SMARCA2 Bryony Thompson Publications for gene: SMARCA2 were set to
Hand and foot malformations v0.43 SMARCA2 Bryony Thompson Classified gene: SMARCA2 as Green List (high evidence)
Hand and foot malformations v0.43 SMARCA2 Bryony Thompson Gene: smarca2 has been classified as Green List (High Evidence).
Hand and foot malformations v0.42 RAD21 Bryony Thompson Marked gene: RAD21 as ready
Hand and foot malformations v0.42 RAD21 Bryony Thompson Gene: rad21 has been classified as Green List (High Evidence).
Hand and foot malformations v0.42 RAD21 Bryony Thompson Classified gene: RAD21 as Green List (high evidence)
Hand and foot malformations v0.42 RAD21 Bryony Thompson Gene: rad21 has been classified as Green List (High Evidence).
Hand and foot malformations v0.41 RAD21 Bryony Thompson Publications for gene: RAD21 were set to
Hand and foot malformations v0.40 PHF6 Bryony Thompson Marked gene: PHF6 as ready
Hand and foot malformations v0.40 PHF6 Bryony Thompson Gene: phf6 has been classified as Green List (High Evidence).
Hand and foot malformations v0.40 PHF6 Bryony Thompson Publications for gene: PHF6 were set to
Hand and foot malformations v0.39 PHF6 Bryony Thompson Mode of inheritance for gene: PHF6 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Hand and foot malformations v0.38 PHF6 Bryony Thompson Classified gene: PHF6 as Green List (high evidence)
Hand and foot malformations v0.38 PHF6 Bryony Thompson Gene: phf6 has been classified as Green List (High Evidence).
Hand and foot malformations v0.37 PHF6 Bryony Thompson edited their review of gene: PHF6: Changed rating: GREEN; Set current diagnostic: yes
Hand and foot malformations v0.37 PHF6 Bryony Thompson reviewed gene: PHF6: Rating: ; Mode of pathogenicity: None; Publications: 19161141, 24092917, 12415272; Phenotypes: Borjeson-Forssman-Lehmann syndrome MIM#301900; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v0.121 GNAO1 Danielle Ariti gene: GNAO1 was added
gene: GNAO1 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: GNAO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GNAO1 were set to 33528536; 34364746; 33098801
Phenotypes for gene: GNAO1 were set to Cerebral Palsy; Neurodevelopmental disorder with involuntary movements MIM# 617493
Review for gene: GNAO1 was set to GREEN
Added comment: >10 individuals in CP cohort reported with mono-allelic (de novo) GNAO1variants.
The majority of these individuals were diagnosed with Dyskinetic CP displaying progressive movement disorder (dystonia, athetosis and chorea), ID and often seizures.
Sources: Expert list
Hand and foot malformations v0.37 NXN Bryony Thompson Marked gene: NXN as ready
Hand and foot malformations v0.37 NXN Bryony Thompson Gene: nxn has been classified as Green List (High Evidence).
Hand and foot malformations v0.37 NXN Bryony Thompson Publications for gene: NXN were set to
Hand and foot malformations v0.36 NXN Bryony Thompson Classified gene: NXN as Green List (high evidence)
Hand and foot malformations v0.36 NXN Bryony Thompson Gene: nxn has been classified as Green List (High Evidence).
Hand and foot malformations v0.35 LTBP2 Bryony Thompson Marked gene: LTBP2 as ready
Hand and foot malformations v0.35 LTBP2 Bryony Thompson Gene: ltbp2 has been classified as Red List (Low Evidence).
Hand and foot malformations v0.35 LTBP2 Bryony Thompson Publications for gene: LTBP2 were set to
Hand and foot malformations v0.34 LTBP2 Bryony Thompson reviewed gene: LTBP2: Rating: RED; Mode of pathogenicity: None; Publications: 22539340; Phenotypes: Weill-Marchesani syndrome 3, recessive MIM#614819; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hand and foot malformations v0.34 KMT2A Bryony Thompson Marked gene: KMT2A as ready
Hand and foot malformations v0.34 KMT2A Bryony Thompson Gene: kmt2a has been classified as Green List (High Evidence).
Hand and foot malformations v0.34 KMT2A Bryony Thompson Publications for gene: KMT2A were set to
Hand and foot malformations v0.33 KMT2A Bryony Thompson Classified gene: KMT2A as Green List (high evidence)
Hand and foot malformations v0.33 KMT2A Bryony Thompson Gene: kmt2a has been classified as Green List (High Evidence).
Hand and foot malformations v0.32 KMT2A Bryony Thompson reviewed gene: KMT2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 22795537, 24886118; Phenotypes: Wiedemann-Steiner syndrome MIM#605130; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hand and foot malformations v0.32 KDM6A Bryony Thompson Marked gene: KDM6A as ready
Hand and foot malformations v0.32 KDM6A Bryony Thompson Gene: kdm6a has been classified as Green List (High Evidence).
Hand and foot malformations v0.32 KDM6A Bryony Thompson Publications for gene: KDM6A were set to
Hand and foot malformations v0.31 KDM6A Bryony Thompson Classified gene: KDM6A as Green List (high evidence)
Hand and foot malformations v0.31 KDM6A Bryony Thompson Gene: kdm6a has been classified as Green List (High Evidence).
Hand and foot malformations v0.30 KDM6A Bryony Thompson reviewed gene: KDM6A: Rating: GREEN; Mode of pathogenicity: None; Publications: 33674768; Phenotypes: Kabuki syndrome 2 MIM#300867, brachydactyly, clinodactyly; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v0.121 FOXG1 Danielle Ariti gene: FOXG1 was added
gene: FOXG1 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: FOXG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXG1 were set to 34077496; 33528536
Phenotypes for gene: FOXG1 were set to Cerebral Palsy; Rett syndrome, congenital variant MIM# 613454
Review for gene: FOXG1 was set to GREEN
Added comment: 5 individuals in CP cohort reported with mono-allelic (de novo) FOXG1 variants.
All individuals presented with movement impairments (3 with Spastic quadriplegia), intellectual disability, and microcephaly (and 2 individuals with seizures).
Sources: Expert list
Mendeliome v0.9219 FMN1 Bryony Thompson Marked gene: FMN1 as ready
Mendeliome v0.9219 FMN1 Bryony Thompson Gene: fmn1 has been classified as Amber List (Moderate Evidence).
Hand and foot malformations v0.30 IFT57 Bryony Thompson Marked gene: IFT57 as ready
Hand and foot malformations v0.30 IFT57 Bryony Thompson Gene: ift57 has been classified as Red List (Low Evidence).
Hand and foot malformations v0.30 IFT57 Bryony Thompson Publications for gene: IFT57 were set to
Lymphoedema v0.11 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Hand and foot malformations v0.29 HDAC4 Bryony Thompson Tag SV/CNV tag was added to gene: HDAC4.
Hand and foot malformations v0.29 HDAC4 Bryony Thompson Publications for gene: HDAC4 were set to
Hand and foot malformations v0.28 HDAC4 Bryony Thompson Classified gene: HDAC4 as Amber List (moderate evidence)
Hand and foot malformations v0.28 HDAC4 Bryony Thompson Gene: hdac4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9219 FMN1 Bryony Thompson Classified gene: FMN1 as Amber List (moderate evidence)
Mendeliome v0.9219 FMN1 Bryony Thompson Gene: fmn1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9218 FMN1 Bryony Thompson gene: FMN1 was added
gene: FMN1 was added to Mendeliome. Sources: Literature
SV/CNV tags were added to gene: FMN1.
Mode of inheritance for gene: FMN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FMN1 were set to 20610440; 19383632; 15202026
Phenotypes for gene: FMN1 were set to oligosyndactyly; radioulnar synostosis; hearing loss; renal defects
Review for gene: FMN1 was set to AMBER
Added comment: A 263 Kb homozygous deletion of FMN1 has been identified in a single case with oligosyndactyly, radioulnar synostosis, hearing loss and renal defects. Also, a supporting null mouse model with oligosyndactyly. Also, a large duplication including GREM1 reported in association with Cenani–Lenz syndrome.
Sources: Literature
Hand and foot malformations v0.27 FMN1 Bryony Thompson Marked gene: FMN1 as ready
Hand and foot malformations v0.27 FMN1 Bryony Thompson Gene: fmn1 has been classified as Amber List (Moderate Evidence).
Hand and foot malformations v0.27 FMN1 Bryony Thompson Phenotypes for gene: FMN1 were changed from to oligosyndactyly; radioulnar synostosis; hearing loss; renal defects
Hand and foot malformations v0.26 FMN1 Bryony Thompson Publications for gene: FMN1 were set to
Hand and foot malformations v0.25 FMN1 Bryony Thompson Mode of inheritance for gene: FMN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Hand and foot malformations v0.24 FMN1 Bryony Thompson Classified gene: FMN1 as Amber List (moderate evidence)
Hand and foot malformations v0.24 FMN1 Bryony Thompson Gene: fmn1 has been classified as Amber List (Moderate Evidence).
Hand and foot malformations v0.23 FMN1 Bryony Thompson Tag SV/CNV tag was added to gene: FMN1.
Hand and foot malformations v0.23 FMN1 Bryony Thompson reviewed gene: FMN1: Rating: AMBER; Mode of pathogenicity: None; Publications: 20610440, 19383632, 15202026; Phenotypes: oligosyndactyly, radioulnar synostosis, hearing loss, renal defects; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9217 LBX1 Zornitza Stark Marked gene: LBX1 as ready
Mendeliome v0.9217 LBX1 Zornitza Stark Gene: lbx1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9217 LBX1 Zornitza Stark Classified gene: LBX1 as Amber List (moderate evidence)
Mendeliome v0.9217 LBX1 Zornitza Stark Gene: lbx1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9216 LBX1 Zornitza Stark gene: LBX1 was added
gene: LBX1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: LBX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LBX1 were set to 30487221
Phenotypes for gene: LBX1 were set to Central hypoventilation syndrome, congenital, 3, MIM#619483
Review for gene: LBX1 was set to AMBER
Added comment: Two siblings reported with homozygous LoF variant in this gene, supportive mouse model.
Sources: Expert Review
Central Hypoventilation v1.3 LBX1 Zornitza Stark Marked gene: LBX1 as ready
Central Hypoventilation v1.3 LBX1 Zornitza Stark Gene: lbx1 has been classified as Amber List (Moderate Evidence).
Central Hypoventilation v1.3 LBX1 Zornitza Stark Classified gene: LBX1 as Amber List (moderate evidence)
Central Hypoventilation v1.3 LBX1 Zornitza Stark Gene: lbx1 has been classified as Amber List (Moderate Evidence).
Central Hypoventilation v1.2 LBX1 Zornitza Stark gene: LBX1 was added
gene: LBX1 was added to Central Hypoventilation. Sources: Expert Review
Mode of inheritance for gene: LBX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LBX1 were set to 30487221
Phenotypes for gene: LBX1 were set to Central hypoventilation syndrome, congenital, 3, MIM#619483
Review for gene: LBX1 was set to AMBER
Added comment: Two siblings reported with homozygous LoF variant in this gene, supportive mouse model.
Sources: Expert Review
Mendeliome v0.9215 FBXW4 Bryony Thompson Phenotypes for gene: FBXW4 were changed from to Split-hand/foot malformation 3 syndrome MIM#246560
Mendeliome v0.9214 B9D1 Bryony Thompson Publications for gene: B9D1 were set to 24886560; 21493627; 25920555
Mendeliome v0.9213 FBXW4 Bryony Thompson Publications for gene: FBXW4 were set to
Mendeliome v0.9212 FBXW4 Bryony Thompson Classified gene: FBXW4 as Red List (low evidence)
Mendeliome v0.9212 FBXW4 Bryony Thompson Gene: fbxw4 has been classified as Red List (Low Evidence).
Mendeliome v0.9211 FBXW4 Bryony Thompson reviewed gene: FBXW4: Rating: RED; Mode of pathogenicity: None; Publications: 12913067, 16235095, 27600068; Phenotypes: Split-hand/foot malformation 3 syndrome MIM#246560; Mode of inheritance: None
Hand and foot malformations v0.23 FBXW4 Bryony Thompson Marked gene: FBXW4 as ready
Hand and foot malformations v0.23 FBXW4 Bryony Thompson Gene: fbxw4 has been classified as Red List (Low Evidence).
Hand and foot malformations v0.23 FBXW4 Bryony Thompson Publications for gene: FBXW4 were set to
Hand and foot malformations v0.22 FBXW4 Bryony Thompson reviewed gene: FBXW4: Rating: RED; Mode of pathogenicity: None; Publications: 12913067, 16235095, 27600068; Phenotypes: Split-hand/foot malformation (SHFM); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hand and foot malformations v0.22 FBLN1 Bryony Thompson Publications for gene: FBLN1 were set to
Hand and foot malformations v0.21 FBLN1 Bryony Thompson Marked gene: FBLN1 as ready
Hand and foot malformations v0.21 FBLN1 Bryony Thompson Gene: fbln1 has been classified as Red List (Low Evidence).
Hand and foot malformations v0.21 FAT1 Bryony Thompson Marked gene: FAT1 as ready
Hand and foot malformations v0.21 FAT1 Bryony Thompson Gene: fat1 has been classified as Green List (High Evidence).
Hand and foot malformations v0.21 FAT1 Bryony Thompson Phenotypes for gene: FAT1 were changed from to facial dysmorphism; colobomatous microphthalmia; ptosis; syndactyly with or without nephropathy
Hand and foot malformations v0.20 FAT1 Bryony Thompson Publications for gene: FAT1 were set to
Hand and foot malformations v0.19 FAT1 Bryony Thompson Mode of inheritance for gene: FAT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Hand and foot malformations v0.18 FAT1 Bryony Thompson Classified gene: FAT1 as Green List (high evidence)
Hand and foot malformations v0.18 FAT1 Bryony Thompson Gene: fat1 has been classified as Green List (High Evidence).
Hand and foot malformations v0.17 EP300 Bryony Thompson Marked gene: EP300 as ready
Hand and foot malformations v0.17 EP300 Bryony Thompson Gene: ep300 has been classified as Green List (High Evidence).
Hand and foot malformations v0.17 EP300 Bryony Thompson Classified gene: EP300 as Green List (high evidence)
Hand and foot malformations v0.17 EP300 Bryony Thompson Added comment: Comment on list classification: Limb anomalies are a feature of Rubinstein-Taybi syndrome
Hand and foot malformations v0.17 EP300 Bryony Thompson Gene: ep300 has been classified as Green List (High Evidence).
Dystonia and Chorea v0.192 IMPDH2 Arina Puzriakova reviewed gene: IMPDH2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34305140; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cerebral Palsy v0.121 PIGN Clare van Eyk changed review comment from: Two cases with compound heterozygous missense variants in PIGN were identified in a retrospective reanalysis of a large Clinical Laboratory referral cohort with cerebral palsy. Limb hypertonia and spasticity have been described in some children with Multiple congenital anomalies-hypotonia-seizures syndrome 1. Most children with Multiple congenital anomalies-hypotonia-seizures syndrome 1 die before 3 years of age, however missense variants have been reported to cause a less severe clinical phenotype.An additional case with a homozygous missense variant in PIGN was described to have atypical cerebral palsy with multiple other anomalies.; to: Two cases with compound heterozygous missense variants in PIGN were identified in a retrospective reanalysis of a large Clinical Laboratory referral cohort with cerebral palsy. Limb hypertonia and spasticity have been described in some children with Multiple congenital anomalies-hypotonia-seizures syndrome 1. Most children with Multiple congenital anomalies-hypotonia-seizures syndrome 1 die before 3 years of age, however missense variants have been reported to cause a less severe clinical phenotype. An additional case with a homozygous missense variant in PIGN was described to have atypical cerebral palsy with multiple other anomalies.
Cerebral Palsy v0.121 PIGN Clare van Eyk Deleted their comment
Cerebral Palsy v0.121 PIGN Clare van Eyk edited their review of gene: PIGN: Added comment: Two cases with compound heterozygous missense variants in PIGN were identified in a retrospective reanalysis of a large Clinical Laboratory referral cohort with cerebral palsy. Limb hypertonia and spasticity have been described in some children with Multiple congenital anomalies-hypotonia-seizures syndrome 1. Most children with Multiple congenital anomalies-hypotonia-seizures syndrome 1 die before 3 years of age, however missense variants have been reported to cause a less severe clinical phenotype.An additional case with a homozygous missense variant in PIGN was described to have atypical cerebral palsy with multiple other anomalies.; Changed rating: GREEN; Changed publications: PMID: 33528536, PMID: 34540776
Cerebral Palsy v0.121 PIGN Clare van Eyk gene: PIGN was added
gene: PIGN was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PIGN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGN were set to PMID: 33528536
Phenotypes for gene: PIGN were set to Multiple congenital anomalies-hypotonia-seizures syndrome 1 (OMIM 614080)
Review for gene: PIGN was set to AMBER
Added comment: Two cases with compound heterozygous missense variants in PIGN were identified in a retrospective reanalysis of a large Clinical Laboratory referral cohort with cerebral palsy. Limb hypertonia and spasticity have been described in some children with Multiple congenital anomalies-hypotonia-seizures syndrome 1. Most children with Multiple congenital anomalies-hypotonia-seizures syndrome 1 die before 3 years of age, however missense variants have been reported to cause a less severe clinical phenotype.
Sources: Literature
Cerebral Palsy v0.121 PCDH19 Clare van Eyk changed review comment from: Variants in PCDH19 cause an X-linked disorder which affects heterozygous females, with hemizygous males largely unaffected. One male with spastic diplegic cerebral palsy described with a hemizygous predicted pathogenic variant.
Sources: Literature; to: Variants in PCDH19 cause an X-linked disorder which affects heterozygous females, with hemizygous males largely unaffected. One male with spastic diplegic cerebral palsy described with a hemizygous predicted pathogenic variant.
Sources: Literature
Cerebral Palsy v0.121 PCDH19 Clare van Eyk gene: PCDH19 was added
gene: PCDH19 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PCDH19 was set to Other
Publications for gene: PCDH19 were set to PMID: 34321325
Phenotypes for gene: PCDH19 were set to Developmental and epileptic encephalopathy 9 (OMIM 300088)
Review for gene: PCDH19 was set to RED
Added comment: Variants in PCDH19 cause an X-linked disorder which affects heterozygous females, with hemizygous males largely unaffected. One male with spastic diplegic cerebral palsy described with a hemizygous predicted pathogenic variant.
Sources: Literature
Cerebral Palsy v0.121 PCDH12 Clare van Eyk gene: PCDH12 was added
gene: PCDH12 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PCDH12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCDH12 were set to PMID: 34321325; PMID: 29556033
Phenotypes for gene: PCDH12 were set to Diencephalic-mesencephalic junction dysplasia syndrome 1 (OMIM 251280)
Review for gene: PCDH12 was set to GREEN
Added comment: One case with homozygous nonsense variant reported with dysmorphic features, dystonic cerebral palsy and comorbidities including intellectual disability. Second individual with compound heterozygous truncating PCDH12 variants diagnosed as dyskinetic cerebral palsy with epilepsy and severe intellectual disability. Biallelic PCDH12 mutations cause a syndromic neurodevelopmental disorder with spasticity or dystonia.
Sources: Literature
Imprinting disorders v0.8 ZFP57 Zornitza Stark Marked gene: ZFP57 as ready
Imprinting disorders v0.8 ZFP57 Zornitza Stark Gene: zfp57 has been classified as Green List (High Evidence).
Imprinting disorders v0.8 ZFP57 Zornitza Stark Publications for gene: ZFP57 were set to 18622393; 23150280; 25848000
Imprinting disorders v0.7 MKRN3 Zornitza Stark reviewed gene: MKRN3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Imprinting disorders v0.7 MKRN3 Zornitza Stark Tag SV/CNV tag was added to gene: MKRN3.
Tag 5'UTR tag was added to gene: MKRN3.
Imprinting disorders v0.7 MKRN3 Zornitza Stark Marked gene: MKRN3 as ready
Imprinting disorders v0.7 MKRN3 Zornitza Stark Gene: mkrn3 has been classified as Green List (High Evidence).
Imprinting disorders v0.7 MKRN3 Zornitza Stark Publications for gene: MKRN3 were set to PMID: 23738509; http://igc.otago.ac.nz/home.html; 30794780
Imprinting disorders v0.6 KCNK9 Zornitza Stark Marked gene: KCNK9 as ready
Imprinting disorders v0.6 KCNK9 Zornitza Stark Gene: kcnk9 has been classified as Green List (High Evidence).
Imprinting disorders v0.6 KCNK9 Zornitza Stark Phenotypes for gene: KCNK9 were changed from Phenotype resulting from under expression: mental retardation, hypotonia, dysmprophism; Affected tissue: brain; Birk-Barel syndrome to Phenotype resulting from under expression: mental retardation, hypotonia, dysmprophism; Affected tissue: brain; Birk-Barel syndrome, MIM# 612292; MONDO:0012856
Imprinting disorders v0.5 KCNK9 Zornitza Stark Publications for gene: KCNK9 were set to http://igc.otago.ac.nz/home.html; PMID: 24667089; 18678320; 30794780
Imprinting disorders v0.4 KCNK9 Zornitza Stark reviewed gene: KCNK9: Rating: GREEN; Mode of pathogenicity: None; Publications: 28333430, 27151206, 24980697, 18678320; Phenotypes: Birk-Barel syndrome, MIM# 612292, MONDO:0012856; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Mendeliome v0.9211 RAF1 Zornitza Stark Marked gene: RAF1 as ready
Mendeliome v0.9211 RAF1 Zornitza Stark Gene: raf1 has been classified as Green List (High Evidence).
Mendeliome v0.9211 RAF1 Zornitza Stark Phenotypes for gene: RAF1 were changed from to Noonan syndrome 5, MIM# 611553; Cardiomyopathy, dilated, 1NN, MIM# 615916
Mendeliome v0.9210 RAF1 Zornitza Stark Publications for gene: RAF1 were set to
Mendeliome v0.9209 RAF1 Zornitza Stark Mode of pathogenicity for gene: RAF1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mendeliome v0.9208 RAF1 Zornitza Stark Mode of inheritance for gene: RAF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9207 RAF1 Zornitza Stark reviewed gene: RAF1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 17603483, 17603482, 31145547, 31030682, 29271604, 24777450; Phenotypes: Noonan syndrome 5, MIM# 611553, Cardiomyopathy, dilated, 1NN, MIM# 615916; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v0.108 RAF1 Zornitza Stark Marked gene: RAF1 as ready
Cardiomyopathy_Paediatric v0.108 RAF1 Zornitza Stark Gene: raf1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.108 RAF1 Zornitza Stark Phenotypes for gene: RAF1 were changed from Noonan syndrome 5; Noonan syndrome 5 611553; LEOPARD syndrome 2 611554; syndromic HCM; LEOPARD syndrome 2; LEOPARD syndrome; Noonan syndrome to Cardiomyopathy, dilated, 1NN, MIM# 615916; Noonan syndrome 5, MIM# 611553
Cardiomyopathy_Paediatric v0.107 RAF1 Zornitza Stark Publications for gene: RAF1 were set to 17603482; 17603483
Cardiomyopathy_Paediatric v0.106 RAF1 Zornitza Stark reviewed gene: RAF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24777450; Phenotypes: Cardiomyopathy, dilated, 1NN, MIM# 615916, Noonan syndrome 5, MIM# 611553; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.213 CDKN1C Zornitza Stark Marked gene: CDKN1C as ready
Differences of Sex Development v0.213 CDKN1C Zornitza Stark Gene: cdkn1c has been classified as Green List (High Evidence).
Differences of Sex Development v0.213 CDKN1C Zornitza Stark Phenotypes for gene: CDKN1C were changed from to IMAGe syndrome, MIM# 614732
Differences of Sex Development v0.212 CDKN1C Zornitza Stark Publications for gene: CDKN1C were set to
Differences of Sex Development v0.211 CDKN1C Zornitza Stark Mode of pathogenicity for gene: CDKN1C was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Differences of Sex Development v0.210 CDKN1C Zornitza Stark Mode of inheritance for gene: CDKN1C was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Differences of Sex Development v0.209 CDKN1C Zornitza Stark reviewed gene: CDKN1C: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 22634751, 33076988, 31976094, 31497289; Phenotypes: IMAGe syndrome, MIM# 614732; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Mendeliome v0.9207 CDKN1C Zornitza Stark Marked gene: CDKN1C as ready
Mendeliome v0.9207 CDKN1C Zornitza Stark Gene: cdkn1c has been classified as Green List (High Evidence).
Mendeliome v0.9207 CDKN1C Zornitza Stark Phenotypes for gene: CDKN1C were changed from to Beckwith-Wiedemann syndrome, MIM# 130650; IMAGe syndrome, MIM# 614732; Silver-Russell syndrome
Mendeliome v0.9206 CDKN1C Zornitza Stark Publications for gene: CDKN1C were set to
Mendeliome v0.9205 CDKN1C Zornitza Stark Mode of inheritance for gene: CDKN1C was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Mendeliome v0.9204 CDKN1C Zornitza Stark reviewed gene: CDKN1C: Rating: GREEN; Mode of pathogenicity: None; Publications: 10424811, 8841187, 22205991, 20503313, 19843502, 15372379, 23511928, 30794780, 33076988, 31976094, 31497289; Phenotypes: Beckwith-Wiedemann syndrome, MIM# 130650, IMAGe syndrome, MIM# 614732, Silver-Russell syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Imprinting disorders v0.4 CDKN1C Zornitza Stark Marked gene: CDKN1C as ready
Imprinting disorders v0.4 CDKN1C Zornitza Stark Gene: cdkn1c has been classified as Green List (High Evidence).
Imprinting disorders v0.4 CDKN1C Zornitza Stark Publications for gene: CDKN1C were set to 10424811; PMID: 8841187; 22205991]; 20503313; 19843502; http://igc.otago.ac.nz/home.html; [15372379; 23511928; 30794780
Imprinting disorders v0.3 CDKN1C Zornitza Stark reviewed gene: CDKN1C: Rating: GREEN; Mode of pathogenicity: None; Publications: 10424811, 8841187, 22205991, 20503313, 19843502, 15372379, 23511928, 30794780, 33076988, 31976094, 31497289; Phenotypes: Beckwith-Wiedemann syndrome, MIM# 130650, IMAGe syndrome, MIM# 614732, Silver-Russell syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Hand and foot malformations v0.16 DYNC1I1 Bryony Thompson Marked gene: DYNC1I1 as ready
Hand and foot malformations v0.16 DYNC1I1 Bryony Thompson Gene: dync1i1 has been classified as Green List (High Evidence).
Hand and foot malformations v0.16 DYNC1I1 Bryony Thompson Phenotypes for gene: DYNC1I1 were changed from to Split-hand/split-foot malformation (SHFM)
Hand and foot malformations v0.15 DYNC1I1 Bryony Thompson Publications for gene: DYNC1I1 were set to
Hand and foot malformations v0.14 DYNC1I1 Bryony Thompson Mode of inheritance for gene: DYNC1I1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hand and foot malformations v0.13 DYNC1I1 Bryony Thompson Tag SV/CNV tag was added to gene: DYNC1I1.
Hand and foot malformations v0.13 DYNC1I1 Bryony Thompson Classified gene: DYNC1I1 as Green List (high evidence)
Hand and foot malformations v0.13 DYNC1I1 Bryony Thompson Gene: dync1i1 has been classified as Green List (High Evidence).
Hand and foot malformations v0.12 DYNC1I1 Bryony Thompson reviewed gene: DYNC1I1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22914741, 25231166, 32219838; Phenotypes: Split-hand/split-foot malformation (SHFM); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hand and foot malformations v0.12 DPF2 Bryony Thompson Marked gene: DPF2 as ready
Hand and foot malformations v0.12 DPF2 Bryony Thompson Gene: dpf2 has been classified as Green List (High Evidence).
Hand and foot malformations v0.12 DPF2 Bryony Thompson Classified gene: DPF2 as Green List (high evidence)
Hand and foot malformations v0.12 DPF2 Bryony Thompson Gene: dpf2 has been classified as Green List (High Evidence).
Hand and foot malformations v0.11 DPF2 Bryony Thompson reviewed gene: DPF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29429572; Phenotypes: Coffin-Siris syndrome 7 MIM#618027; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hand and foot malformations v0.11 DLX6 Bryony Thompson Marked gene: DLX6 as ready
Hand and foot malformations v0.11 DLX6 Bryony Thompson Gene: dlx6 has been classified as Red List (Low Evidence).
Hand and foot malformations v0.11 DLX6 Bryony Thompson Phenotypes for gene: DLX6 were changed from Split-hand/foot malformation 1 183600; Split-hand/foot malformation 1 with sensorineural hearing loss 220600 to Split-hand/foot malformation 1 183600
Hand and foot malformations v0.10 DLX6 Bryony Thompson Publications for gene: DLX6 were set to
Hand and foot malformations v0.9 DLX6 Bryony Thompson Mode of inheritance for gene: DLX6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hand and foot malformations v0.8 DLX6 Bryony Thompson reviewed gene: DLX6: Rating: RED; Mode of pathogenicity: None; Publications: 28611547; Phenotypes: Split-hand and foot malformation (SHFM, MIM 183600); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hand and foot malformations v0.8 CHUK Bryony Thompson Marked gene: CHUK as ready
Hand and foot malformations v0.8 CHUK Bryony Thompson Gene: chuk has been classified as Amber List (Moderate Evidence).
Hand and foot malformations v0.8 CHUK Bryony Thompson Publications for gene: CHUK were set to
Hand and foot malformations v0.7 CHUK Bryony Thompson Mode of inheritance for gene: CHUK was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hand and foot malformations v0.6 CHUK Bryony Thompson Classified gene: CHUK as Amber List (moderate evidence)
Hand and foot malformations v0.6 CHUK Bryony Thompson Gene: chuk has been classified as Amber List (Moderate Evidence).
Hand and foot malformations v0.5 ARHGAP31 Bryony Thompson Marked gene: ARHGAP31 as ready
Hand and foot malformations v0.5 ARHGAP31 Bryony Thompson Gene: arhgap31 has been classified as Green List (High Evidence).
Hand and foot malformations v0.5 ARHGAP31 Bryony Thompson Publications for gene: ARHGAP31 were set to
Hand and foot malformations v0.4 ARHGAP31 Bryony Thompson reviewed gene: ARHGAP31: Rating: GREEN; Mode of pathogenicity: None; Publications: 21565291, 24668619, 29924900; Phenotypes: Adams-Oliver syndrome 1 MIM#100300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9204 B9D1 Bryony Thompson Classified gene: B9D1 as Green List (high evidence)
Mendeliome v0.9204 B9D1 Bryony Thompson Gene: b9d1 has been classified as Green List (High Evidence).
Mendeliome v0.9203 B9D1 Bryony Thompson changed review comment from: hNow N
PMID: 34338422 - compound het missense and frameshift variant in a proband with anal atresia with vestibular fistula, ventricular septal defect, and right renal agenesis (VACTERL cohort)
PMID: 21763481 - B9d1 -/- mouse displayed polydactyly, kidney cysts, ductal plate malformations, and abnormal patterning of the neural tube, concomitant with compromised ciliogenesis, ciliary protein localization, and Hedgehog (Hh) signal transduction.; to: 3 unrelated cases with a syndromic phenotype and a supporting null mouse model
PMID: 34338422 - compound het missense and frameshift variant in a proband with anal atresia with vestibular fistula, ventricular septal defect, and right renal agenesis (VACTERL cohort)
PMID: 24886560 - 2 Joubert syndrome cases
PMID: 21763481 - B9d1 -/- mouse displayed polydactyly, kidney cysts, ductal plate malformations, and abnormal patterning of the neural tube, concomitant with compromised ciliogenesis, ciliary protein localization, and Hedgehog (Hh) signal transduction.
Mendeliome v0.9203 B9D1 Bryony Thompson reviewed gene: B9D1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21763481, 24886560, 34338422; Phenotypes: Meckel syndrome, Joubert syndrome, VACTERL; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9203 LEFTY2 Elena Savva reviewed gene: LEFTY2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 10518210, 10053005; Phenotypes: Heterotaxy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hand and foot malformations v0.4 Bryony Thompson removed gene:B9D1 from the panel
Hand and foot malformations v0.1 Bryony Thompson Panel types changed to Royal Melbourne Hospital; Rare Disease
Hand and foot malformations v0.0 WNT5A Bryony Thompson gene: WNT5A was added
gene: WNT5A was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: WNT5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: WNT5A were set to Robinow syndrome, autosomal dominant 1 180700
Hand and foot malformations v0.0 WNT3 Bryony Thompson gene: WNT3 was added
gene: WNT3 was added to Hand and foot malformation. Sources: Expert list
Mode of inheritance for gene: WNT3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WNT3 were set to Tetra-amelia syndrome 273395
Hand and foot malformations v0.0 WNT10B Bryony Thompson gene: WNT10B was added
gene: WNT10B was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: WNT10B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WNT10B were set to Split-hand/foot malformation 6 225300
Hand and foot malformations v0.0 TRPV4 Bryony Thompson gene: TRPV4 was added
gene: TRPV4 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: TRPV4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TRPV4 were set to Parastremmatic dwarfism 168400; Metatropic dysplasia 156530; Spinal muscular atrophy, distal, congenital nonprogressive 600175; Scapuloperoneal spinal muscular atrophy 181405; SED, Maroteaux type 184095; Spondylometaphyseal dysplasia, Kozlowski type 184252; Hereditary motor and sensory neuropathy, type IIc 606071; Brachyolmia type 3 113500; Digital arthropathy-brachydactyly, familial 606835
Hand and foot malformations v0.0 TRPS1 Bryony Thompson gene: TRPS1 was added
gene: TRPS1 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: TRPS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TRPS1 were set to Trichorhinophalangeal syndrome, type III 190351; Trichorhinophalangeal syndrome, type I 190350
Hand and foot malformations v0.0 TP63 Bryony Thompson gene: TP63 was added
gene: TP63 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: TP63 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TP63 were set to Hay-Wells syndrome 106260; Rapp-Hodgkin syndrome 129400; Limb-mammary syndrome 603543; Split-hand/foot malformation 4 605289; Orofacial cleft 8 129400; ULT syndrome 103285; Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 604292
Hand and foot malformations v0.0 TGDS Bryony Thompson gene: TGDS was added
gene: TGDS was added to Hand and foot malformation. Sources: Expert list
Mode of inheritance for gene: TGDS was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TGDS were set to Catel-Manzke syndrome 616145
Hand and foot malformations v0.0 TBX15 Bryony Thompson gene: TBX15 was added
gene: TBX15 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: TBX15 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TBX15 were set to Cousin syndrome 260660
Hand and foot malformations v0.0 SOX9 Bryony Thompson gene: SOX9 was added
gene: SOX9 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: SOX9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SOX9 were set to Campomelic dysplasia with autosomal sex reversal 114290
Hand and foot malformations v0.0 SOST Bryony Thompson gene: SOST was added
gene: SOST was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: SOST was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: SOST were set to Van Buchem disease 239100; Sclerosteosis 1 269500; Craniodiaphyseal dysplasia, autosomal dominant 122860
Hand and foot malformations v0.0 SMC3 Bryony Thompson gene: SMC3 was added
gene: SMC3 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: SMC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SMC3 were set to Cornelia de Lange syndrome 3 610759
Hand and foot malformations v0.0 SMC1A Bryony Thompson gene: SMC1A was added
gene: SMC1A was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: SMC1A was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: SMC1A were set to Cornelia de Lange syndrome 2 300590
Hand and foot malformations v0.0 SMARCE1 Bryony Thompson gene: SMARCE1 was added
gene: SMARCE1 was added to Hand and foot malformation. Sources: Expert list
Mode of inheritance for gene: SMARCE1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SMARCE1 were set to Coffin-Siris syndrome 5 MIM#616938
Hand and foot malformations v0.0 SMARCB1 Bryony Thompson gene: SMARCB1 was added
gene: SMARCB1 was added to Hand and foot malformation. Sources: Expert list
Mode of inheritance for gene: SMARCB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SMARCB1 were set to Coffin-Siris syndrome 3 MIM#614608
Hand and foot malformations v0.0 SMARCA4 Bryony Thompson gene: SMARCA4 was added
gene: SMARCA4 was added to Hand and foot malformation. Sources: Expert list
Mode of inheritance for gene: SMARCA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SMARCA4 were set to Coffin-Siris syndrome 4 MIM#614609
Hand and foot malformations v0.0 SMARCA2 Bryony Thompson gene: SMARCA2 was added
gene: SMARCA2 was added to Hand and foot malformation. Sources: Expert list
Mode of inheritance for gene: SMARCA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SMARCA2 were set to Nicolaides-Baraitser syndrome MIM#601358
Hand and foot malformations v0.0 SMAD4 Bryony Thompson gene: SMAD4 was added
gene: SMAD4 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: SMAD4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SMAD4 were set to Myhre syndrome 139210
Hand and foot malformations v0.0 SF3B4 Bryony Thompson gene: SF3B4 was added
gene: SF3B4 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: SF3B4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SF3B4 were set to Acrofacial dysostosis 1, Nager type 154400
Hand and foot malformations v0.0 ROR2 Bryony Thompson gene: ROR2 was added
gene: ROR2 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: ROR2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: ROR2 were set to Robinow syndrome, autosomal recessive 268310; Brachydactyly, type B1 113000
Hand and foot malformations v0.0 RECQL4 Bryony Thompson gene: RECQL4 was added
gene: RECQL4 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: RECQL4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RECQL4 were set to Rothmund-Thomson syndrome 268400; RAPILINO syndrome 266280; Baller-Gerold syndrome 218600
Hand and foot malformations v0.0 RBPJ Bryony Thompson gene: RBPJ was added
gene: RBPJ was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: RBPJ was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RBPJ were set to Adams-Oliver syndrome 3, 614814
Hand and foot malformations v0.0 RBM8A Bryony Thompson gene: RBM8A was added
gene: RBM8A was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: RBM8A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RBM8A were set to Thrombocytopenia-absent radius syndrome 274000
Hand and foot malformations v0.0 RAD21 Bryony Thompson gene: RAD21 was added
gene: RAD21 was added to Hand and foot malformation. Sources: Expert list
Mode of inheritance for gene: RAD21 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RAD21 were set to Cornelia de Lange syndrome 4 614701
Hand and foot malformations v0.0 PTHLH Bryony Thompson gene: PTHLH was added
gene: PTHLH was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: PTHLH was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PTHLH were set to Brachydactyly, type E2 613382
Hand and foot malformations v0.0 PTDSS1 Bryony Thompson gene: PTDSS1 was added
gene: PTDSS1 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: PTDSS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PTDSS1 were set to Lenz-Majewski hyperostotic dwarfism 151050
Hand and foot malformations v0.0 PRMT7 Bryony Thompson gene: PRMT7 was added
gene: PRMT7 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: PRMT7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PRMT7 were set to Short stature, brachydactyly, intellectual developmental disability, and seizures 617157
Hand and foot malformations v0.0 PRKAR1A Bryony Thompson gene: PRKAR1A was added
gene: PRKAR1A was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: PRKAR1A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: PRKAR1A were set to Myxoma, intracardiac 255960; Acrodysostosis 1, with or without hormone resistance 101800; Pigmented nodular adrenocortical disease, primary, 1 610489
Hand and foot malformations v0.0 POLR1A Bryony Thompson gene: POLR1A was added
gene: POLR1A was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: POLR1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: POLR1A were set to Acrofacial dysostosis, Cincinnati type 616462
Hand and foot malformations v0.0 PIGV Bryony Thompson gene: PIGV was added
gene: PIGV was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: PIGV was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PIGV were set to Hyperphosphatasia with mental retardation syndrome 1 239300
Hand and foot malformations v0.0 PHF6 Bryony Thompson gene: PHF6 was added
gene: PHF6 was added to Hand and foot malformation. Sources: Expert list
Mode of inheritance for gene: PHF6 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: PHF6 were set to Borjeson-Forssman-Lehmann syndrome MIM#301900
Hand and foot malformations v0.0 PGM3 Bryony Thompson gene: PGM3 was added
gene: PGM3 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: PGM3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PGM3 were set to Immunodeficiency 23 615816
Hand and foot malformations v0.0 PDE4D Bryony Thompson gene: PDE4D was added
gene: PDE4D was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: PDE4D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PDE4D were set to Acrodysostosis 2, with or without hormone resistance 614613
Hand and foot malformations v0.0 PDE3A Bryony Thompson gene: PDE3A was added
gene: PDE3A was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: PDE3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PDE3A were set to Hypertension and brachydactyly syndrome, 112410
Hand and foot malformations v0.0 NXN Bryony Thompson gene: NXN was added
gene: NXN was added to Hand and foot malformation. Sources: Expert list
Mode of inheritance for gene: NXN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NXN were set to Robinow syndrome, autosomal recessive 2 MIM#618529
Hand and foot malformations v0.0 NSDHL Bryony Thompson gene: NSDHL was added
gene: NSDHL was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: NSDHL was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: NSDHL were set to CK syndrome 300831; Congenital hemidysplasia, ichthyosis, limb defects (CHILD) syndrome 308050
Hand and foot malformations v0.0 NOTCH1 Bryony Thompson gene: NOTCH1 was added
gene: NOTCH1 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: NOTCH1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: NOTCH1 were set to Limb, scalp and skull defects; AOS; Adams-Oliver syndrome 5, 616028; Combination of aplasia cutis congenita of the scalp vertex and terminal transverse limb defects (e.g., amputations, syndactyly, brachydactyly, or oligodactyly)
Hand and foot malformations v0.0 NOG Bryony Thompson gene: NOG was added
gene: NOG was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: NOG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NOG were set to Stapes ankylosis with broad thumb and toes 184460; Symphalangism, proximal, 1A 185800; Multiple synostoses syndrome 1 186500; Tarsal-carpal coalition syndrome 186570; Brachydactyly, type B2 611377
Hand and foot malformations v0.0 NIPBL Bryony Thompson gene: NIPBL was added
gene: NIPBL was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: NIPBL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NIPBL were set to Cornelia de Lange syndrome 1 122470
Hand and foot malformations v0.0 NECTIN4 Bryony Thompson gene: NECTIN4 was added
gene: NECTIN4 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: NECTIN4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NECTIN4 were set to Ectodermal dysplasia-syndactyly syndrome 1 MIM#613573
Hand and foot malformations v0.0 NECTIN1 Bryony Thompson gene: NECTIN1 was added
gene: NECTIN1 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: NECTIN1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NECTIN1 were set to Cleft lip/palate-ectodermal dysplasia syndrome MIM#225060
Hand and foot malformations v0.0 MYCN Bryony Thompson gene: MYCN was added
gene: MYCN was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: MYCN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MYCN were set to Feingold syndrome (Microcephaly-oculo-digito-esophageal-duodenal) 164280
Hand and foot malformations v0.0 MGP Bryony Thompson gene: MGP was added
gene: MGP was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: MGP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MGP were set to Keutel syndrome 245150
Hand and foot malformations v0.0 LTBP3 Bryony Thompson gene: LTBP3 was added
gene: LTBP3 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: LTBP3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: LTBP3 were set to Geleophysic dysplasia 3 617809; Dental anomalies and short stature 610216
Hand and foot malformations v0.0 LTBP2 Bryony Thompson gene: LTBP2 was added
gene: LTBP2 was added to Hand and foot malformation. Sources: Expert list
Mode of inheritance for gene: LTBP2 was set to Unknown
Phenotypes for gene: LTBP2 were set to Weill-Marchesani
Hand and foot malformations v0.0 LRP4 Bryony Thompson gene: LRP4 was added
gene: LRP4 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: LRP4 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: LRP4 were set to Sclerosteosis 2 614305; Cenani-Lenz syndactyly syndrome 212780
Hand and foot malformations v0.0 KMT2D Bryony Thompson gene: KMT2D was added
gene: KMT2D was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: KMT2D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: KMT2D were set to Kabuki syndrome 1 - 147920
Hand and foot malformations v0.0 KMT2A Bryony Thompson gene: KMT2A was added
gene: KMT2A was added to Hand and foot malformation. Sources: Expert list
Mode of inheritance for gene: KMT2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KMT2A were set to Wiedemann-Steiner syndrome MIM#605130
Hand and foot malformations v0.0 KDM6A Bryony Thompson gene: KDM6A was added
gene: KDM6A was added to Hand and foot malformation. Sources: Expert list
Mode of inheritance for gene: KDM6A was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: KDM6A were set to Kabuki syndrome 2 MIM#300867
Hand and foot malformations v0.0 IHH Bryony Thompson gene: IHH was added
gene: IHH was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: IHH was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: IHH were set to Brachydactyly, type A1 112500; Acrocapitofemoral dysplasia 607778
Hand and foot malformations v0.0 IFT57 Bryony Thompson gene: IFT57 was added
gene: IFT57 was added to Hand and foot malformation. Sources: Expert list
Mode of inheritance for gene: IFT57 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IFT57 were set to ?Orofaciodigital syndrome XVIII MIM#617927
Hand and foot malformations v0.0 HDAC8 Bryony Thompson gene: HDAC8 was added
gene: HDAC8 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: HDAC8 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: HDAC8 were set to Wilson-Turner syndrome 309585; Cornelia de Lange syndrome 5 300882
Hand and foot malformations v0.0 HDAC4 Bryony Thompson gene: HDAC4 was added
gene: HDAC4 was added to Hand and foot malformation. Sources: Expert list
Mode of inheritance for gene: HDAC4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: HDAC4 were set to Albright hereditary osteodystrophy-like syndrome; Brachydactyly-intellectual disability
Hand and foot malformations v0.0 GSC Bryony Thompson gene: GSC was added
gene: GSC was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: GSC was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GSC were set to Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities, MIM# 602471
Hand and foot malformations v0.0 GNAS Bryony Thompson gene: GNAS was added
gene: GNAS was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: GNAS was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Phenotypes for gene: GNAS were set to McCune-Albright syndrome, somatic, mosaic 174800; ACTH-independent macronodular adrenal hyperplasia 219080 IC; Osseous heteroplasia, progressive 166350; Pseudohypoparathyroidism Ic 612462; Pseudopseudohypoparathyroidism 612463; Pseudohypoparathyroidism Ia 103580; Pseudohypoparathyroidism Ib 603233
Hand and foot malformations v0.0 GJA1 Bryony Thompson gene: GJA1 was added
gene: GJA1 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: GJA1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: GJA1 were set to Hypoplastic left heart syndrome 1 241550; Syndactyly, type III 186100; Oculodentodigital dysplasia 164200; Palmoplantar keratoderma with congenital alopecia 104100; Craniometaphyseal dysplasia, autosomal recessive 218400; Erythrokeratodermia variabilis et progressiva 133200; Oculodentodigital dysplasia, autosomal recessive 257850
Hand and foot malformations v0.0 GDF6 Bryony Thompson gene: GDF6 was added
gene: GDF6 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: GDF6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: GDF6 were set to Multiple synostoses syndrome type 4 - 617898.; Klippel-Feil syndrome 1, autosomal dominant 118100
Hand and foot malformations v0.0 FZD2 Bryony Thompson gene: FZD2 was added
gene: FZD2 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: FZD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FZD2 were set to Autosomal dominant omodysplasia 164745; Autosomal dominant omodysplasia type 2 164745
Hand and foot malformations v0.0 FMN1 Bryony Thompson gene: FMN1 was added
gene: FMN1 was added to Hand and foot malformation. Sources: Expert list
Mode of inheritance for gene: FMN1 was set to Unknown
Hand and foot malformations v0.0 FLNA Bryony Thompson gene: FLNA was added
gene: FLNA was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: FLNA was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: FLNA were set to Osteodysplasty Melnick Needles 309350 XLD; Otopalatodigital syndrome, type II 304120 XLD; Frontometaphyseal dysplasia 305620; Terminal osseous dysplasia 300244; Otopalatodigital syndrome, type I -311300
Hand and foot malformations v0.0 FIG4 Bryony Thompson gene: FIG4 was added
gene: FIG4 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: FIG4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FIG4 were set to Yunis-Varon syndrome 216340; Amyotrophic lateral sclerosis 11 612577
Hand and foot malformations v0.0 FGF9 Bryony Thompson gene: FGF9 was added
gene: FGF9 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: FGF9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FGF9 were set to Multiple synostoses syndrome type 3 612961
Hand and foot malformations v0.0 FBXW4 Bryony Thompson gene: FBXW4 was added
gene: FBXW4 was added to Hand and foot malformation. Sources: Expert list
Mode of inheritance for gene: FBXW4 was set to Unknown
Phenotypes for gene: FBXW4 were set to Split-hand/foot malformation 3 syndrome 246560
Hand and foot malformations v0.0 FBN1 Bryony Thompson gene: FBN1 was added
gene: FBN1 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: FBN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FBN1 were set to Marfan syndrome 154700; Weill-Marchesani syndrome 2, dominant 608328; Stiff skin syndrome 184900; Acromicric dysplasia 102370; Geleophysic dysplasia 2 614185
Hand and foot malformations v0.0 FBLN1 Bryony Thompson gene: FBLN1 was added
gene: FBLN1 was added to Hand and foot malformation. Sources: Expert list
Mode of inheritance for gene: FBLN1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: FBLN1 were set to Synpolydactyly, 3/3'4, associated with metacarpal and metatarsal synostoses 608180
Hand and foot malformations v0.0 FAT1 Bryony Thompson gene: FAT1 was added
gene: FAT1 was added to Hand and foot malformation. Sources: Expert list
Mode of inheritance for gene: FAT1 was set to Unknown
Hand and foot malformations v0.0 ESCO2 Bryony Thompson gene: ESCO2 was added
gene: ESCO2 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: ESCO2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ESCO2 were set to SC phocomelia syndrome 269000; Roberts syndrome 268300
Hand and foot malformations v0.0 EP300 Bryony Thompson gene: EP300 was added
gene: EP300 was added to Hand and foot malformation. Sources: Expert list
Mode of inheritance for gene: EP300 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: EP300 were set to Rubinstein-Taybi syndrome 180849
Hand and foot malformations v0.0 EOGT Bryony Thompson gene: EOGT was added
gene: EOGT was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: EOGT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EOGT were set to Adams Oliver syndrome 4
Hand and foot malformations v0.0 DYNC1I1 Bryony Thompson gene: DYNC1I1 was added
gene: DYNC1I1 was added to Hand and foot malformation. Sources: Expert list
Mode of inheritance for gene: DYNC1I1 was set to Unknown
Hand and foot malformations v0.0 DVL3 Bryony Thompson gene: DVL3 was added
gene: DVL3 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: DVL3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DVL3 were set to Robinow syndrome, autosomal dominant 3, 616894
Hand and foot malformations v0.0 DVL1 Bryony Thompson gene: DVL1 was added
gene: DVL1 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: DVL1 was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Phenotypes for gene: DVL1 were set to Robinow syndrome, autosomal dominant 2, MIM# 616331
Hand and foot malformations v0.0 DPF2 Bryony Thompson gene: DPF2 was added
gene: DPF2 was added to Hand and foot malformation. Sources: Expert list
Mode of inheritance for gene: DPF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DPF2 were set to Coffin-Siris syndrome 7 MIM#618027
Hand and foot malformations v0.0 DOCK6 Bryony Thompson gene: DOCK6 was added
gene: DOCK6 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: DOCK6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DOCK6 were set to Adams-Oliver syndrome 2 614219
Hand and foot malformations v0.0 DLX6 Bryony Thompson gene: DLX6 was added
gene: DLX6 was added to Hand and foot malformation. Sources: Expert list
Mode of inheritance for gene: DLX6 was set to Unknown
Phenotypes for gene: DLX6 were set to Split-hand/foot malformation 1 183600; Split-hand/foot malformation 1 with sensorineural hearing loss 220600
Hand and foot malformations v0.0 DLX5 Bryony Thompson gene: DLX5 was added
gene: DLX5 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: DLX5 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: DLX5 were set to Split-hand/foot malformation 1 with sensorineural hearing loss 220600
Hand and foot malformations v0.0 DLL4 Bryony Thompson gene: DLL4 was added
gene: DLL4 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: DLL4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DLL4 were set to Adams-Oliver syndrome 6, 616589
Hand and foot malformations v0.0 DHODH Bryony Thompson gene: DHODH was added
gene: DHODH was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: DHODH was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DHODH were set to Miller syndrome (postaxial acrofacial dysostosis) 263750
Hand and foot malformations v0.0 DHCR7 Bryony Thompson gene: DHCR7 was added
gene: DHCR7 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: DHCR7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DHCR7 were set to Smith-Lemli-Opitz syndrome 270400
Hand and foot malformations v0.0 CREBBP Bryony Thompson gene: CREBBP was added
gene: CREBBP was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: CREBBP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CREBBP were set to Rubinstein-Taybi syndrome 180849
Hand and foot malformations v0.0 CHUK Bryony Thompson gene: CHUK was added
gene: CHUK was added to Hand and foot malformation. Sources: Expert list
Mode of inheritance for gene: CHUK was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CHUK were set to ?Popliteal pterygium syndrome, Bartsocas-Papas type 2 MIM#619339; Cocoon syndrome MIM#613630
Hand and foot malformations v0.0 CHSY1 Bryony Thompson gene: CHSY1 was added
gene: CHSY1 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: CHSY1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CHSY1 were set to Temtamy preaxial brachydactyly syndrome 605282
Hand and foot malformations v0.0 CDH3 Bryony Thompson gene: CDH3 was added
gene: CDH3 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: CDH3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CDH3 were set to Ectodermal dysplasia, ectrodactyly, and macular dystrophy 225280
Hand and foot malformations v0.0 FAM58A Bryony Thompson gene: FAM58A was added
gene: FAM58A was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: FAM58A was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: FAM58A were set to STAR syndrome 300707
Hand and foot malformations v0.0 CACNA1C Bryony Thompson gene: CACNA1C was added
gene: CACNA1C was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: CACNA1C was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: CACNA1C were set to Timothy syndrome MIM#601005
Hand and foot malformations v0.0 BMPR1B Bryony Thompson gene: BMPR1B was added
gene: BMPR1B was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: BMPR1B was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: BMPR1B were set to Acromesomelic dysplasia, Demirhan type 609441; Brachydactyly, type A1, D 616849; Brachydactyly, type A2 112600
Hand and foot malformations v0.0 BMP2 Bryony Thompson gene: BMP2 was added
gene: BMP2 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: BMP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: BMP2 were set to Brachydactyly, type A2 112600; short stature, facial dysmorphism and skeletal anomalies with or without cardiac aomalies 617877.
Hand and foot malformations v0.0 B9D1 Bryony Thompson gene: B9D1 was added
gene: B9D1 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: B9D1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: B9D1 were set to Meckel syndrome 9 614209
Hand and foot malformations v0.0 B3GLCT Bryony Thompson gene: B3GLCT was added
gene: B3GLCT was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: B3GLCT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: B3GLCT were set to O-fucose-specific beta-1,3-N-glucosyltransferase deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies); Peters-plus syndrome 261540
Hand and foot malformations v0.0 ARID1B Bryony Thompson gene: ARID1B was added
gene: ARID1B was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: ARID1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ARID1B were set to Coffin-Siris syndrome type 1 - 135900
Hand and foot malformations v0.0 ARID1A Bryony Thompson gene: ARID1A was added
gene: ARID1A was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: ARID1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ARID1A were set to Coffin-Siris
Hand and foot malformations v0.0 ARHGAP31 Bryony Thompson gene: ARHGAP31 was added
gene: ARHGAP31 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: ARHGAP31 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ARHGAP31 were set to Adams-Oliver syndrome 1 100300
Hand and foot malformations v0.0 ANKRD11 Bryony Thompson gene: ANKRD11 was added
gene: ANKRD11 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: ANKRD11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ANKRD11 were set to KBG syndrome 148050
Hand and foot malformations v0.0 AFF4 Bryony Thompson gene: AFF4 was added
gene: AFF4 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: AFF4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: AFF4 were set to CHOPS syndrome MIM#616368
Hand and foot malformations v0.0 ADAMTS17 Bryony Thompson gene: ADAMTS17 was added
gene: ADAMTS17 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: ADAMTS17 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ADAMTS17 were set to Weill-Marchesani syndrome type 4
Hand and foot malformations v0.0 ADAMTS10 Bryony Thompson gene: ADAMTS10 was added
gene: ADAMTS10 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: ADAMTS10 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ADAMTS10 were set to Weill-Marchesani syndrome 1, recessive, 277600
Hand and foot malformations v0.0 ACVR1 Bryony Thompson gene: ACVR1 was added
gene: ACVR1 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: ACVR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ACVR1 were set to Fibrodysplasia ossificans progressiva 135100
Hand and foot malformations v0.0 Bryony Thompson Added panel Hand and foot malformation
Polydactyly v0.240 TMEM107 Bryony Thompson Classified gene: TMEM107 as Green List (high evidence)
Polydactyly v0.240 TMEM107 Bryony Thompson Gene: tmem107 has been classified as Green List (High Evidence).
Polydactyly v0.239 TMEM107 Bryony Thompson gene: TMEM107 was added
gene: TMEM107 was added to Polydactyly. Sources: Expert list
Mode of inheritance for gene: TMEM107 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM107 were set to 22698544; 26123494; 26518474
Phenotypes for gene: TMEM107 were set to Meckel syndrome 13 MIM#617562; Orofaciodigital syndrome XVI MIM#617563
Review for gene: TMEM107 was set to GREEN
gene: TMEM107 was marked as current diagnostic
Added comment: At least four unrelated families with polydactyly as a feature of the condition and a supporting null mouse model.
Sources: Expert list
Polydactyly v0.238 MAP3K20 Bryony Thompson Marked gene: MAP3K20 as ready
Polydactyly v0.238 MAP3K20 Bryony Thompson Gene: map3k20 has been classified as Green List (High Evidence).
Polydactyly v0.238 MAP3K20 Bryony Thompson Classified gene: MAP3K20 as Green List (high evidence)
Polydactyly v0.238 MAP3K20 Bryony Thompson Gene: map3k20 has been classified as Green List (High Evidence).
Polydactyly v0.237 MAP3K20 Bryony Thompson gene: MAP3K20 was added
gene: MAP3K20 was added to Polydactyly. Sources: Expert list
Mode of inheritance for gene: MAP3K20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAP3K20 were set to 26755636; 32266845
Phenotypes for gene: MAP3K20 were set to Split-foot malformation with mesoaxial polydactyly MIM#616890
Review for gene: MAP3K20 was set to GREEN
Added comment: PMID: 26755636 - Polydactyly is a feature of the condition in two consanguineous families with homozygous variants. A mouse model recapitulates the phenotype.
PMID: 32266845 - A heterozygous missense was identified in a case with split hand/foot malformation (SHFM), but also large deletion including SHFM-causing genes is also present
Sources: Expert list
Cerebral Palsy v0.118 ECHS1 Zornitza Stark Marked gene: ECHS1 as ready
Cerebral Palsy v0.118 ECHS1 Zornitza Stark Gene: echs1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.118 ECHS1 Zornitza Stark Classified gene: ECHS1 as Green List (high evidence)
Cerebral Palsy v0.118 ECHS1 Zornitza Stark Gene: echs1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.117 EARS2 Zornitza Stark Marked gene: EARS2 as ready
Cerebral Palsy v0.117 EARS2 Zornitza Stark Gene: ears2 has been classified as Green List (High Evidence).
Cerebral Palsy v0.117 EARS2 Zornitza Stark Classified gene: EARS2 as Green List (high evidence)
Cerebral Palsy v0.117 EARS2 Zornitza Stark Gene: ears2 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.121 ARID1B Bryony Thompson Marked gene: ARID1B as ready
Skeletal dysplasia v0.121 ARID1B Bryony Thompson Gene: arid1b has been classified as Green List (High Evidence).
Skeletal dysplasia v0.121 ARID1B Bryony Thompson Publications for gene: ARID1B were set to
Skeletal dysplasia v0.120 ARID1B Bryony Thompson Mode of inheritance for gene: ARID1B was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v0.119 ARID1B Bryony Thompson changed review comment from: Skeletal limb anomalies, spinal anomalies, and short stature have been reported as a feature of the condition. >3 cases reported.; to: Skeletal limb anomalies, spinal anomalies, and short stature have been reported as a feature of the condition. >3 cases reported, at least one case identified in a skeletal dysplasia cohort.
Skeletal dysplasia v0.119 ARID1B Bryony Thompson Classified gene: ARID1B as Green List (high evidence)
Skeletal dysplasia v0.119 ARID1B Bryony Thompson Gene: arid1b has been classified as Green List (High Evidence).
Skeletal dysplasia v0.118 ARID1B Bryony Thompson changed review comment from: Skeletal limb anomalies, spinal anomalies, and short stature have been reported as a feature of the condition. > cases reported.; to: Skeletal limb anomalies, spinal anomalies, and short stature have been reported as a feature of the condition. >3 cases reported.
Skeletal dysplasia v0.118 ARID1B Bryony Thompson reviewed gene: ARID1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 22426308, 23929686, 34122524; Phenotypes: Coffin-Siris syndrome 1 MIM#135900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Skeletal dysplasia v0.118 ARID1A Bryony Thompson Marked gene: ARID1A as ready
Skeletal dysplasia v0.118 ARID1A Bryony Thompson Gene: arid1a has been classified as Green List (High Evidence).
Skeletal dysplasia v0.118 ARID1A Bryony Thompson Publications for gene: ARID1A were set to
Skeletal dysplasia v0.117 ARID1A Bryony Thompson Mode of inheritance for gene: ARID1A was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v0.116 ARID1A Bryony Thompson Classified gene: ARID1A as Green List (high evidence)
Skeletal dysplasia v0.116 ARID1A Bryony Thompson Gene: arid1a has been classified as Green List (High Evidence).
Skeletal dysplasia v0.115 ARID1A Bryony Thompson changed review comment from: At least 5 cases have been reported with skeletal anomalies as a feature of the condition. Mosaicism is very common for the gene.; to: At least 5 cases have been reported with skeletal anomalies (brachydactyly and polydactyly) as a feature of the condition. Mosaicism is very common for the gene.
Skeletal dysplasia v0.115 ARID1A Bryony Thompson reviewed gene: ARID1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 22426308, 23929686, 32888375; Phenotypes: Coffin-Siris syndrome 2 MM#614607; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Cerebral Palsy v0.116 ECHS1 Danielle Ariti gene: ECHS1 was added
gene: ECHS1 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: ECHS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ECHS1 were set to 33528536; 34364746; 32858208
Phenotypes for gene: ECHS1 were set to Cerebral Palsy; Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency MIM# 616277
Review for gene: ECHS1 was set to GREEN
Added comment: Two cases in CP cohort reported with compound heterozygous ECHS1variants.
One of the individuals presented with delayed motor skills with coordination problems, dystonia (at age 11), and spasticity in upper and lower limbs.

ECHS1 variants cause an inborn error of metabolism disorder characterised by severely delayed psychomotor development, neurodegeneration, increased lactic acid, and brain lesions in the basal ganglia. Some of these cases display paroxysmal and non-paroxysmal dystonia.
Sources: Expert list
Cerebral Palsy v0.116 EARS2 Danielle Ariti gene: EARS2 was added
gene: EARS2 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: EARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EARS2 were set to 33528536; 34364746
Phenotypes for gene: EARS2 were set to Cerebral Palsy; Combined oxidative phosphorylation deficiency 12 MIM# 614924
Review for gene: EARS2 was set to GREEN
Added comment: Two individuals in CP cohort reported with bi-allelic EARS2 variants.
One of the individuals presented with severe ID, ASD and seizures on top of impaired motor symptoms.

Overlapping CP phenotype with COXPD12- mitochondrial neurologic disorder characterised by onset in infancy of hypotonia and delayed psychomotor development, or early developmental regression. Severe cases can present with Dystonia, Spastic tetraparesis and/or lack of speech.
Sources: Expert list
Genetic Epilepsy v0.1195 SPEN Zornitza Stark Marked gene: SPEN as ready
Genetic Epilepsy v0.1195 SPEN Zornitza Stark Gene: spen has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1195 SPEN Zornitza Stark Classified gene: SPEN as Amber List (moderate evidence)
Genetic Epilepsy v0.1195 SPEN Zornitza Stark Gene: spen has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.130 SPEN Zornitza Stark Marked gene: SPEN as ready
Congenital Heart Defect v0.130 SPEN Zornitza Stark Gene: spen has been classified as Green List (High Evidence).
Congenital Heart Defect v0.130 SPEN Zornitza Stark Classified gene: SPEN as Green List (high evidence)
Congenital Heart Defect v0.130 SPEN Zornitza Stark Gene: spen has been classified as Green List (High Evidence).
Autism v0.168 SPEN Zornitza Stark Marked gene: SPEN as ready
Autism v0.168 SPEN Zornitza Stark Gene: spen has been classified as Green List (High Evidence).
Autism v0.168 SPEN Zornitza Stark Classified gene: SPEN as Green List (high evidence)
Autism v0.168 SPEN Zornitza Stark Gene: spen has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.93 SPEN Zornitza Stark Marked gene: SPEN as ready
Deafness_IsolatedAndComplex v1.93 SPEN Zornitza Stark Gene: spen has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v1.93 SPEN Zornitza Stark Classified gene: SPEN as Amber List (moderate evidence)
Deafness_IsolatedAndComplex v1.93 SPEN Zornitza Stark Gene: spen has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.115 AFF4 Bryony Thompson Marked gene: AFF4 as ready
Skeletal dysplasia v0.115 AFF4 Bryony Thompson Gene: aff4 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.115 AFF4 Bryony Thompson Classified gene: AFF4 as Green List (high evidence)
Skeletal dysplasia v0.115 AFF4 Bryony Thompson Gene: aff4 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.114 AFF4 Bryony Thompson gene: AFF4 was added
gene: AFF4 was added to Skeletal dysplasia. Sources: Other
Mode of inheritance for gene: AFF4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AFF4 were set to 25730767; 31058441
Phenotypes for gene: AFF4 were set to CHOPS syndrome MIM#616368
Mode of pathogenicity for gene: AFF4 was set to Other
Review for gene: AFF4 was set to GREEN
gene: AFF4 was marked as current diagnostic
Added comment: CHOPS syndrome: C for Cognitive impairment and Coarse facies, H for Heart defects, O for Obesity, P for Pulmonary involvement and S for Short stature and Skeletal dysplasia. 8 out of 11 cases had skeletal dysplasia as a feature of the condition. Gain-of-function is the mechanism of disease.
Sources: Other
Cerebral Palsy v0.116 DDX3X Zornitza Stark Marked gene: DDX3X as ready
Cerebral Palsy v0.116 DDX3X Zornitza Stark Gene: ddx3x has been classified as Green List (High Evidence).
Cerebral Palsy v0.116 DDX3X Zornitza Stark Classified gene: DDX3X as Green List (high evidence)
Cerebral Palsy v0.116 DDX3X Zornitza Stark Gene: ddx3x has been classified as Green List (High Evidence).
Cerebral Palsy v0.115 DDHD2 Zornitza Stark Marked gene: DDHD2 as ready
Cerebral Palsy v0.115 DDHD2 Zornitza Stark Gene: ddhd2 has been classified as Green List (High Evidence).
Cerebral Palsy v0.115 DDHD2 Zornitza Stark Classified gene: DDHD2 as Green List (high evidence)
Cerebral Palsy v0.115 DDHD2 Zornitza Stark Gene: ddhd2 has been classified as Green List (High Evidence).
Cerebral Palsy v0.114 DDX3X Danielle Ariti gene: DDX3X was added
gene: DDX3X was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: DDX3X was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: DDX3X were set to 33528536
Phenotypes for gene: DDX3X were set to Cerebral Palsy; Intellectual developmental disorder, X-linked, syndrome, Snijders Blok type MIM# 300958
Review for gene: DDX3X was set to GREEN
Added comment: 6 individuals in CP cohort reported with de novo DDX3X variants.
Sources: Expert list
Cerebral Palsy v0.114 DDHD2 Danielle Ariti gene: DDHD2 was added
gene: DDHD2 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: DDHD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDHD2 were set to 30705080; 34077496; 34321325
Phenotypes for gene: DDHD2 were set to Cerebral Palsy; Spastic paraplegia 54, autosomal recessive MIM# 615033
Review for gene: DDHD2 was set to GREEN
Added comment: Two individuals reported in CP cohort. Phenotype-Spastic diplegia, and ID.

Multiple reports of CP-mimic patients with global developmental delay and non-progressive spastic gait.

SPG54 individuals display CP-like phenotype such as intellectual disability, early-onset spasticity of the lower limbs and delayed psychomotor development.
Sources: Expert list
Cerebral Palsy v0.114 DDC Zornitza Stark Marked gene: DDC as ready
Cerebral Palsy v0.114 DDC Zornitza Stark Added comment: Comment when marking as ready: Phenotypic overlap with CP: ID and movement disorders
Cerebral Palsy v0.114 DDC Zornitza Stark Gene: ddc has been classified as Green List (High Evidence).
Cerebral Palsy v0.114 DDC Zornitza Stark Classified gene: DDC as Green List (high evidence)
Cerebral Palsy v0.114 DDC Zornitza Stark Gene: ddc has been classified as Green List (High Evidence).
Cerebral Palsy v0.113 CYP2U1 Zornitza Stark Marked gene: CYP2U1 as ready
Cerebral Palsy v0.113 CYP2U1 Zornitza Stark Gene: cyp2u1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.113 CYP2U1 Zornitza Stark Classified gene: CYP2U1 as Green List (high evidence)
Cerebral Palsy v0.113 CYP2U1 Zornitza Stark Gene: cyp2u1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.112 COL4A2 Zornitza Stark Marked gene: COL4A2 as ready
Cerebral Palsy v0.112 COL4A2 Zornitza Stark Gene: col4a2 has been classified as Green List (High Evidence).
Cerebral Palsy v0.112 COL4A2 Zornitza Stark Classified gene: COL4A2 as Green List (high evidence)
Cerebral Palsy v0.112 COL4A2 Zornitza Stark Gene: col4a2 has been classified as Green List (High Evidence).
Cerebral Palsy v0.111 DDC Danielle Ariti gene: DDC was added
gene: DDC was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: DDC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDC were set to 33528536; 30799092; 33996177
Phenotypes for gene: DDC were set to Aromatic L-amino acid decarboxylase deficiency MIM# 608643
Review for gene: DDC was set to AMBER
Added comment: Single case reported in CP cohort with Dystonic cerebral palsy.

Multiple AADCD cases reported as CP- mimics due to phenotype overlap: dystonia and developmental delay.

AADCD being is an inborn error in neurotransmitter metabolism disorder that leads to combined serotonin and catecholamine deficiency. Clinically characterised by vegetative symptoms, oculogyric crises, dystonia, and severe neurologic dysfunction (infancy/ early childhood); displays CP-like features.
Sources: Expert list
Genetic Epilepsy v0.1194 SPEN Elena Savva gene: SPEN was added
gene: SPEN was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SPEN was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SPEN were set to PMID: 33596411
Phenotypes for gene: SPEN were set to Radio-Tartaglia syndrome MIM#619312
Review for gene: SPEN was set to AMBER
gene: SPEN was marked as current diagnostic
Added comment: PMID: 33596411
- 34 individuals with truncating variants in SPEN reported, most are de novo variants.
- Clinical profile includes developmental delay/intellectual disability, autism spectrum disorder, anxiety, aggressive behavior, attention deficit disorder, hypotonia, brain and spine anomalies, congenital heart defects, high/narrow palate, facial dysmorphisms, and obesity/increased BMI, especially in females.
- Authors showed haploinsufficiency of SPEN is associated with a distinctive DNA methylation episignature of the X chromosome in affected females.

Seizures were observed in only 3/32 (~9%) of patients
Sources: Literature
Autism v0.167 SPEN Elena Savva gene: SPEN was added
gene: SPEN was added to Autism. Sources: Literature
Mode of inheritance for gene: SPEN was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SPEN were set to PMID: 33596411
Phenotypes for gene: SPEN were set to Radio-Tartaglia syndrome MIM#619312
Review for gene: SPEN was set to GREEN
gene: SPEN was marked as current diagnostic
Added comment: PMID: 33596411
- 34 individuals with truncating variants in SPEN reported, most are de novo variants.
- Clinical profile includes developmental delay/intellectual disability, autism spectrum disorder, anxiety, aggressive behavior, attention deficit disorder, hypotonia, brain and spine anomalies, congenital heart defects, high/narrow palate, facial dysmorphisms, and obesity/increased BMI, especially in females.
- Authors showed haploinsufficiency of SPEN is associated with a distinctive DNA methylation episignature of the X chromosome in affected females.
Sources: Literature
Congenital Heart Defect v0.129 SPEN Elena Savva gene: SPEN was added
gene: SPEN was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: SPEN was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SPEN were set to PMID: 33596411
Phenotypes for gene: SPEN were set to Radio-Tartaglia syndrome MIM#619312
Review for gene: SPEN was set to GREEN
gene: SPEN was marked as current diagnostic
Added comment: PMID: 33596411
- 34 individuals with truncating variants in SPEN reported, most are de novo variants.
- Clinical profile includes developmental delay/intellectual disability, autism spectrum disorder, anxiety, aggressive behavior, attention deficit disorder, hypotonia, brain and spine anomalies, congenital heart defects, high/narrow palate, facial dysmorphisms, and obesity/increased BMI, especially in females.
- Authors showed haploinsufficiency of SPEN is associated with a distinctive DNA methylation episignature of the X chromosome in affected females.
Sources: Literature
Deafness_IsolatedAndComplex v1.92 SPEN Elena Savva gene: SPEN was added
gene: SPEN was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: SPEN was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SPEN were set to PMID: 33596411
Phenotypes for gene: SPEN were set to Radio-Tartaglia syndrome MIM#619312
Review for gene: SPEN was set to AMBER
Added comment: PMID: 33596411
- 34 individuals with truncating variants in SPEN reported, most are de novo variants.
- Clinical profile includes developmental delay/intellectual disability, autism spectrum disorder, anxiety, aggressive behavior, attention deficit disorder, hypotonia, brain and spine anomalies, congenital heart defects, high/narrow palate, facial dysmorphisms, and obesity/increased BMI, especially in females.
- Authors showed haploinsufficiency of SPEN is associated with a distinctive DNA methylation episignature of the X chromosome in affected females.

Hearing loss reported in ~10% of patients, uncommon phenotype
Sources: Literature
Cerebral Palsy v0.111 CYP2U1 Danielle Ariti changed review comment from: Single case reported in CP cohort (bi-allelic c.A947T variant).

SPG56 is an autosomal recessive neurodegenerative disorder characterised by early-onset progressive lower-limb spasticity. 4 reported SPG56 cases display CP-like phenotype: ID and spastic diplegia.
Sources: Expert list; to: Single case reported in CP cohort (bi-allelic p.D316V variant).

SPG56 is an autosomal recessive neurodegenerative disorder characterised by early-onset progressive lower-limb spasticity. 4 reported SPG56 cases display CP-like phenotype: ID and spastic diplegia.
Sources: Expert list
Cerebral Palsy v0.111 CYP2U1 Danielle Ariti gene: CYP2U1 was added
gene: CYP2U1 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: CYP2U1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP2U1 were set to 33528536; 29761117; 23176821
Phenotypes for gene: CYP2U1 were set to Cerebral Palsy; Spastic paraplegia 56, autosomal recessive MIM# 615030
Review for gene: CYP2U1 was set to GREEN
Added comment: Single case reported in CP cohort (bi-allelic c.A947T variant).

SPG56 is an autosomal recessive neurodegenerative disorder characterised by early-onset progressive lower-limb spasticity. 4 reported SPG56 cases display CP-like phenotype: ID and spastic diplegia.
Sources: Expert list
Imprinting disorders v0.3 NLRP5 Anna Le Fevre reviewed gene: NLRP5: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26323243, 31829238, 29574422, 30877238, 32222962, 34440388; Phenotypes: Miscarriage, Beckwith-Wiedemann syndrome, Multi locus imprinting disturbance in offspring; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cerebral Palsy v0.111 COL4A2 Danielle Ariti gene: COL4A2 was added
gene: COL4A2 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: COL4A2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: COL4A2 were set to 33528536; 33912663
Phenotypes for gene: COL4A2 were set to Cerebral Palsy; Brain small vessel disease 2 MIM# 614483
Review for gene: COL4A2 was set to GREEN
Added comment: 7 individuals in CP cohort have been reported with mono-allelic COL4A2 variants. Phenotypic overlap: Spastic Triplegia, ID (no language), porencephaly and seizures.

2 siblings reported with bi-allelic variants; Spastic Cerebral Palsy with ID and Epilepsy.
Sources: Expert list
Cerebral Palsy v0.111 ATL1 Zornitza Stark Phenotypes for gene: ATL1 were changed from Cerebral palsy; Spastic paraplegia 3A, autosomal dominant (OMIM 182600 ) to Cerebral palsy; Spastic paraplegia 3A, autosomal dominant (OMIM 182600 )
Cerebral Palsy v0.111 ATL1 Zornitza Stark Phenotypes for gene: ATL1 were changed from Cerebral palsy to Cerebral palsy; Spastic paraplegia 3A, autosomal dominant (OMIM 182600 )
Cerebral Palsy v0.110 ATL1 Zornitza Stark Publications for gene: ATL1 were set to PMID: 32989326
Cerebral Palsy v0.109 ATL1 Zornitza Stark Classified gene: ATL1 as Green List (high evidence)
Cerebral Palsy v0.109 ATL1 Zornitza Stark Gene: atl1 has been classified as Green List (High Evidence).
Imprinting disorders v0.3 ZNF445 Anna Le Fevre gene: ZNF445 was added
gene: ZNF445 was added to Imprinting disorders. Sources: Literature
Mode of inheritance for gene: ZNF445 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF445 were set to PMID: 34039421; 30602440; 30846001
Phenotypes for gene: ZNF445 were set to Temple syndrome; Multi locus imprinting disturbance (MLID)
Penetrance for gene: ZNF445 were set to unknown
Review for gene: ZNF445 was set to AMBER
Added comment: Suggested rating: AMBER

Single report (Kagami 2021) of a child with Temple syndrome and MLID found to have a novel homozygous truncating variant in ZNF445. ZNF445 has been shown to play a critical role in the maintenance of postfertilisation methylation imprints (Takahashi 2019). Mechanism and parent of origin effects remain uncertain.
Sources: Literature
Cerebral Palsy v0.107 NGLY1 Zornitza Stark Marked gene: NGLY1 as ready
Cerebral Palsy v0.107 NGLY1 Zornitza Stark Gene: ngly1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.107 NGLY1 Zornitza Stark Classified gene: NGLY1 as Green List (high evidence)
Cerebral Palsy v0.107 NGLY1 Zornitza Stark Gene: ngly1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.106 NEXMIF Zornitza Stark Marked gene: NEXMIF as ready
Cerebral Palsy v0.106 NEXMIF Zornitza Stark Gene: nexmif has been classified as Red List (Low Evidence).
Cerebral Palsy v0.106 NEXMIF Zornitza Stark Classified gene: NEXMIF as Red List (low evidence)
Cerebral Palsy v0.106 NEXMIF Zornitza Stark Gene: nexmif has been classified as Red List (Low Evidence).
Cerebral Palsy v0.105 PANK2 Zornitza Stark Marked gene: PANK2 as ready
Cerebral Palsy v0.105 PANK2 Zornitza Stark Gene: pank2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v0.105 PANK2 Zornitza Stark Classified gene: PANK2 as Amber List (moderate evidence)
Cerebral Palsy v0.105 PANK2 Zornitza Stark Gene: pank2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v0.104 NDUFAF2 Zornitza Stark Marked gene: NDUFAF2 as ready
Cerebral Palsy v0.104 NDUFAF2 Zornitza Stark Gene: ndufaf2 has been classified as Green List (High Evidence).
Cerebral Palsy v0.104 NDUFAF2 Zornitza Stark Phenotypes for gene: NDUFAF2 were changed from Cerebral palsy to Cerebral palsy; Mitochondrial complex I deficiency nuclear type 10 (OMIM 618233)
Cerebral Palsy v0.103 NDUFAF2 Zornitza Stark Classified gene: NDUFAF2 as Green List (high evidence)
Cerebral Palsy v0.103 NDUFAF2 Zornitza Stark Gene: ndufaf2 has been classified as Green List (High Evidence).
Cerebral Palsy v0.102 NDUFA12 Zornitza Stark Marked gene: NDUFA12 as ready
Cerebral Palsy v0.102 NDUFA12 Zornitza Stark Gene: ndufa12 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v0.102 NDUFA12 Zornitza Stark Classified gene: NDUFA12 as Amber List (moderate evidence)
Cerebral Palsy v0.102 NDUFA12 Zornitza Stark Gene: ndufa12 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v0.101 NALCN Zornitza Stark Marked gene: NALCN as ready
Cerebral Palsy v0.101 NALCN Zornitza Stark Gene: nalcn has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v0.101 NALCN Zornitza Stark Phenotypes for gene: NALCN were changed from Cerebral palsy to Cerebral palsy; Congenital contractures of the limbs and face, hypotonia, and developmental delay (OMIM 616266)
Cerebral Palsy v0.100 NALCN Zornitza Stark Classified gene: NALCN as Amber List (moderate evidence)
Cerebral Palsy v0.100 NALCN Zornitza Stark Gene: nalcn has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v0.99 ATL1 Clare van Eyk reviewed gene: ATL1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33528536, PMID: 34321325; Phenotypes: Spastic paraplegia 3A, autosomal dominant (OMIM 182600 ); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v0.99 NALCN Clare van Eyk edited their review of gene: NALCN: Changed phenotypes: Congenital contractures of the limbs and face, hypotonia, and developmental delay (OMIM 616266)
Cerebral Palsy v0.99 NDUFA12 Clare van Eyk Deleted their comment
Cerebral Palsy v0.99 NDUFA12 Clare van Eyk edited their review of gene: NDUFA12: Added comment: Mitochondrial disorder causing motor dysfunction with learning difficulties (OMIM 618244). One case in cerebral palsy cohort.; Changed phenotypes: Mitochondrial complex I deficiency, nuclear type 23 (OMIM 618244)
Cerebral Palsy v0.99 NEXMIF Clare van Eyk Deleted their comment
Cerebral Palsy v0.99 NEXMIF Clare van Eyk edited their review of gene: NEXMIF: Added comment: Variants cause X-linked intellectual disability 98 (OMIM:300912). Developmental and epileptic encephalopathy with some affected individuals having movement phenotypes which could be considered CP-like, but did not find any published reports in CP cohorts to date.; Changed phenotypes: X-linked intellectual disability 98 (OMIM:300912)
Cerebral Palsy v0.99 PANK2 Clare van Eyk gene: PANK2 was added
gene: PANK2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PANK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PANK2 were set to PMID: 33098801
Phenotypes for gene: PANK2 were set to HARP syndrome ( OMIM 607236); Neurodegeneration with brain iron accumulation 1 (OMIM 234200)
Review for gene: PANK2 was set to AMBER
Added comment: One case reported with dystonic cerebral palsy. Dystonia and spasticity are reported in cases with variants in PANK2.
Sources: Literature
Cerebral Palsy v0.99 NGLY1 Clare van Eyk gene: NGLY1 was added
gene: NGLY1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NGLY1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NGLY1 were set to PMID:33528536
Phenotypes for gene: NGLY1 were set to Congenital disorder of deglycosylation (OMIM 615273)
Review for gene: NGLY1 was set to GREEN
Added comment: Three cases with biallelic P/LP variants reported in Clinical Laboratory Referral Cohort retrospectively analysed for genetic determinants of cerebral palsy. Autosomal recessive, multisystem disorder with some overlapping clinical features with cerebral palsy, but this is a progressive condition.
Sources: Literature
Cerebral Palsy v0.99 NDUFAF2 Clare van Eyk reviewed gene: NDUFAF2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:33528536, PMID:34364746; Phenotypes: mitochondrial complex I deficiency nuclear type 10 (OMIM 618233); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v0.99 NDUFAF2 Clare van Eyk Deleted their review
Cerebral Palsy v0.99 NEXMIF Clare van Eyk changed review comment from: Variants cause X-linked intellectual disability 98 (OMIM:300912). Developmental and epileptic encephalopathy with some affected individuals having movement phenotypes which could be considered CP-like, but did not find any reports in CP cohorts to date.
Sources: Expert list; to: Variants cause X-linked intellectual disability 98 (OMIM:300912). Developmental and epileptic encephalopathy with some affected individuals having movement phenotypes which could be considered CP-like, but did not find any published reports in CP cohorts to date.
Sources: Expert list
Cerebral Palsy v0.99 NEXMIF Clare van Eyk gene: NEXMIF was added
gene: NEXMIF was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: NEXMIF was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: NEXMIF were set to X-linked Intellectual disability; epilepsy; autism
Penetrance for gene: NEXMIF were set to Incomplete
Review for gene: NEXMIF was set to RED
Added comment: Variants cause X-linked intellectual disability 98 (OMIM:300912). Developmental and epileptic encephalopathy with some affected individuals having movement phenotypes which could be considered CP-like, but did not find any reports in CP cohorts to date.
Sources: Expert list
Cerebral Palsy v0.99 NDUFAF2 Clare van Eyk changed review comment from: Two homozygous pathogenic deletions reported in cerebral palsy cohorts. Biallelic loss of function variants cause mitochondrial complex I deficiency nuclear type 10 (OMIM 618233). Most variants are LOF. Overlapping clinical phenotype.
Sources: Literature; to: Two homozygous pathogenic deletions reported in cerebral palsy cohorts. Biallelic loss of function variants cause mitochondrial complex I deficiency nuclear type 10 (OMIM 618233). Overlapping clinical phenotype.
Sources: Literature
Cerebral Palsy v0.99 NDUFAF2 Clare van Eyk changed review comment from: Two homozygous pathogenic deletions reported in cerebral palsy cohorts. Biallelic loss of function variants cause mitochondrial complex I deficiency nuclear type 10 (OMIM 618233).
Sources: Literature; to: Two homozygous pathogenic deletions reported in cerebral palsy cohorts. Biallelic loss of function variants cause mitochondrial complex I deficiency nuclear type 10 (OMIM 618233). Most variants are LOF. Overlapping clinical phenotype.
Sources: Literature
Cerebral Palsy v0.99 NDUFAF2 Clare van Eyk gene: NDUFAF2 was added
gene: NDUFAF2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NDUFAF2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFAF2 were set to PMID:33528536; PMID:34364746
Phenotypes for gene: NDUFAF2 were set to Cerebral palsy
Review for gene: NDUFAF2 was set to GREEN
Added comment: Two homozygous pathogenic deletions reported in cerebral palsy cohorts. Biallelic loss of function variants cause mitochondrial complex I deficiency nuclear type 10 (OMIM 618233).
Sources: Literature
Cerebral Palsy v0.99 NDUFA12 Clare van Eyk gene: NDUFA12 was added
gene: NDUFA12 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NDUFA12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFA12 were set to PMID:34364746
Phenotypes for gene: NDUFA12 were set to Spastic tetraparesis; intellectual disability; encephalopathy
Review for gene: NDUFA12 was set to AMBER
Added comment: Mitochondrial disorder causing motor dysfunction with learning difficulties (OMIM 618244). One case in cerebral palsy cohort.
Sources: Literature
Cerebral Palsy v0.99 NALCN Clare van Eyk reviewed gene: NALCN: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID:33528536, PMID:34364746; Phenotypes: Cerebral palsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v0.99 NALCN Clare van Eyk Deleted their review
Cerebral Palsy v0.99 NALCN Clare van Eyk gene: NALCN was added
gene: NALCN was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NALCN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NALCN were set to PMID:33528536; 34364746
Phenotypes for gene: NALCN were set to Cerebral palsy
Review for gene: NALCN was set to AMBER
Added comment: One case with pathogenic variant from clinical laboratory referral cohort. One additional VUS from tertiary care setting. NALCN variants cause a congenital disorder with contractures of the limbs, abnormal facial features, hypotonia, and developmental delay (OMIM: 611549). Cerebral palsy has not been described previously.
Sources: Literature
Mendeliome v0.9203 CARMIL2 Zornitza Stark Marked gene: CARMIL2 as ready
Mendeliome v0.9203 CARMIL2 Zornitza Stark Gene: carmil2 has been classified as Green List (High Evidence).
Mendeliome v0.9203 CARMIL2 Zornitza Stark Phenotypes for gene: CARMIL2 were changed from to Immunodeficiency 58, MIM# 618131; Early onset paediatric inflammatory bowel disease
Mendeliome v0.9202 CARMIL2 Zornitza Stark Publications for gene: CARMIL2 were set to
Mendeliome v0.9201 CARMIL2 Zornitza Stark Mode of inheritance for gene: CARMIL2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9200 CARMIL2 Zornitza Stark reviewed gene: CARMIL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29479355, 28112205, 27896283, 33723309; Phenotypes: Immunodeficiency 58, MIM# 618131, Early onset paediatric inflammatory bowel disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Inflammatory bowel disease v0.61 CARMIL2 Zornitza Stark Marked gene: CARMIL2 as ready
Inflammatory bowel disease v0.61 CARMIL2 Zornitza Stark Gene: carmil2 has been classified as Green List (High Evidence).
Inflammatory bowel disease v0.61 CARMIL2 Zornitza Stark Classified gene: CARMIL2 as Green List (high evidence)
Inflammatory bowel disease v0.61 CARMIL2 Zornitza Stark Gene: carmil2 has been classified as Green List (High Evidence).
Inflammatory bowel disease v0.60 CARMIL2 Zornitza Stark gene: CARMIL2 was added
gene: CARMIL2 was added to Inflammatory bowel disease. Sources: Expert Review
Mode of inheritance for gene: CARMIL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CARMIL2 were set to 33723309
Phenotypes for gene: CARMIL2 were set to Early onset paediatric inflammatory bowel disease
Review for gene: CARMIL2 was set to GREEN
Added comment: Bi-allelic variants in this gene are associated with immunodeficiency. Four individuals from three families reported with early onset IBD. None manifested overt clinical signs of immunodeficiency before their diagnosis.
Sources: Expert Review
Cerebral vascular malformations v0.23 SETD5 Bryony Thompson Classified gene: SETD5 as Amber List (moderate evidence)
Cerebral vascular malformations v0.23 SETD5 Bryony Thompson Gene: setd5 has been classified as Amber List (Moderate Evidence).
Cerebral vascular malformations v0.22 CHD4 Bryony Thompson Classified gene: CHD4 as Amber List (moderate evidence)
Cerebral vascular malformations v0.22 CHD4 Bryony Thompson Gene: chd4 has been classified as Amber List (Moderate Evidence).
Cerebral vascular malformations v0.21 ABCC6 Bryony Thompson Marked gene: ABCC6 as ready
Cerebral vascular malformations v0.21 ABCC6 Bryony Thompson Gene: abcc6 has been classified as Red List (Low Evidence).
Cerebral vascular malformations v0.21 ABCC6 Bryony Thompson reviewed gene: ABCC6: Rating: RED; Mode of pathogenicity: None; Publications: 16086762; Phenotypes: Moya moya disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9200 PNLDC1 Zornitza Stark Marked gene: PNLDC1 as ready
Mendeliome v0.9200 PNLDC1 Zornitza Stark Gene: pnldc1 has been classified as Green List (High Evidence).
Mendeliome v0.9200 PNLDC1 Zornitza Stark Classified gene: PNLDC1 as Green List (high evidence)
Mendeliome v0.9200 PNLDC1 Zornitza Stark Gene: pnldc1 has been classified as Green List (High Evidence).
Mendeliome v0.9199 PNLDC1 Zornitza Stark gene: PNLDC1 was added
gene: PNLDC1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: PNLDC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNLDC1 were set to 34347949
Phenotypes for gene: PNLDC1 were set to Spermatogenic failure 57, MIM# 619528
Review for gene: PNLDC1 was set to GREEN
Added comment: Four unrelated individuals reported.
Sources: Expert Review
Mendeliome v0.9198 FOXP1 Zornitza Stark Marked gene: FOXP1 as ready
Mendeliome v0.9198 FOXP1 Zornitza Stark Gene: foxp1 has been classified as Green List (High Evidence).
Mendeliome v0.9198 FOXP1 Zornitza Stark Phenotypes for gene: FOXP1 were changed from to Mental retardation with language impairment and with or without autistic features, MIM# 613670
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.88 FOXP1 Zornitza Stark Marked gene: FOXP1 as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.88 FOXP1 Zornitza Stark Gene: foxp1 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.88 FOXP1 Zornitza Stark Classified gene: FOXP1 as Green List (high evidence)
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.88 FOXP1 Zornitza Stark Gene: foxp1 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.87 FOXP1 Zornitza Stark gene: FOXP1 was added
gene: FOXP1 was added to Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic. Sources: Expert Review
Mode of inheritance for gene: FOXP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXP1 were set to 27657687
Phenotypes for gene: FOXP1 were set to Mental retardation with language impairment and with or without autistic features, MIM# 613670
Review for gene: FOXP1 was set to GREEN
Added comment: Well established association with syndromic ID. Multiple individuals reported with congenital anomalies of the kidneys and urinary tract in PMID 27657687.
Sources: Expert Review
Congenital Heart Defect v0.129 ZMYM2 Zornitza Stark Marked gene: ZMYM2 as ready
Congenital Heart Defect v0.129 ZMYM2 Zornitza Stark Gene: zmym2 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.129 ZMYM2 Zornitza Stark Classified gene: ZMYM2 as Green List (high evidence)
Congenital Heart Defect v0.129 ZMYM2 Zornitza Stark Gene: zmym2 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.128 ZMYM2 Zornitza Stark gene: ZMYM2 was added
gene: ZMYM2 was added to Congenital Heart Defect. Sources: Expert Review
Mode of inheritance for gene: ZMYM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZMYM2 were set to 32891193
Phenotypes for gene: ZMYM2 were set to Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities, MIM# 619522
Review for gene: ZMYM2 was set to GREEN
Added comment: Connaughton et al (2020 - PMID: 32891193) report on 19 individuals (from 15 unrelated families) with heterozygous pathogenic ZMYM2 variants.

Affected individuals from 7 families presented with CAKUT while all of them displayed extra-renal features. Neurological manifestations were reported in 16 individuals from 14 families (data not available for 1 fam), among others hypotonia (3/14 fam), speech delay (4/14 fam), global DD (9/14 fam), ID (4/14 fam), microcephaly (4/14 fam). ASD was reported in 4 fam (4 indiv). Seizures were reported in 2 fam (2 indiv). Variable other features included cardiac defects, facial dysmorphisms, small hands and feet with dys-/hypo-plastic nails and clinodactyly.

14 pLoF variants were identified, in most cases as de novo events (8 fam). In 2 families the variant was inherited from an affected parent. Germline mosaicism occurred in 1 family.

The human disease features were recapitulated in a X. tropicalis morpholino knockdown, with expression of truncating variants failing to rescue renal and craniofacial defects. Heterozygous Zmym2-deficient mice also recapitulated the features of CAKUT.

ZMYM2 (previously ZNF198) encodes a nuclear zinc finger protein localizing to the nucleus (and PML nuclear body).

It has previously been identified as transcriptional corepressor interacting with nuclear receptors and the LSD1-CoREST-HDAC1 complex. It has also been shown to interact with FOXP transcription factors.

The authors provide evidence for loss of interaction of the truncated ZMYM2 with FOXP1 (mutations in the latter having recently been reported in syndromic CAKUT).
Sources: Expert Review
Mendeliome v0.9197 ZMYM2 Zornitza Stark edited their review of gene: ZMYM2: Changed phenotypes: Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities, MIM# 619522
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.86 ZMYM2 Zornitza Stark Phenotypes for gene: ZMYM2 were changed from Abnormality of the urinary system; Global developmental delay; Intellectual disability; Microcephaly; Abnormality of the cardiovascular system; Autism; Seizures; Abnormality of the head or neck; Abnormality of the nail; Small hand; Short foot; Clinodactyly to Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities, MIM# 619522
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.85 ZMYM2 Zornitza Stark reviewed gene: ZMYM2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities, MIM# 619522; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.4130 ZMYM2 Zornitza Stark Phenotypes for gene: ZMYM2 were changed from Abnormality of the urinary system; Global developmental delay; Intellectual disability; Microcephaly; Abnormality of the cardiovascular system; Autism; Seizures; Abnormality of the head or neck; Abnormality of the nail; Small hand; Short foot; Clinodactyly to Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities, MIM# 619522
Intellectual disability syndromic and non-syndromic v0.4129 ZMYM2 Zornitza Stark edited their review of gene: ZMYM2: Changed phenotypes: Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities, MIM# 619522
Mendeliome v0.9197 HCN2 Zornitza Stark Phenotypes for gene: HCN2 were changed from Genetic epilepsy with febrile seizures plus; Other seizure disorders to Febrile seizures, familial, 2, MIM# 602477; Genetic epilepsy with febrile seizures plus; Other seizure disorders
Mendeliome v0.9196 HCN2 Zornitza Stark edited their review of gene: HCN2: Changed phenotypes: Febrile seizures, familial, 2, MIM# 602477, Genetic epilepsy with febrile seizures plus, Other seizure disorders
Genetic Epilepsy v0.1194 HCN2 Zornitza Stark Phenotypes for gene: HCN2 were changed from Genetic epilepsy with febrile seizures plus; Other seizure disorders to Febrile seizures, familial, 2, MIM# 602477; Genetic epilepsy with febrile seizures plus; Other seizure disorders
Genetic Epilepsy v0.1193 HCN2 Zornitza Stark edited their review of gene: HCN2: Changed phenotypes: Febrile seizures, familial, 2, MIM# 602477, Genetic epilepsy with febrile seizures plus, Other seizure disorders
Mendeliome v0.9196 HSCB Zornitza Stark Marked gene: HSCB as ready
Mendeliome v0.9196 HSCB Zornitza Stark Gene: hscb has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9196 HSCB Zornitza Stark Classified gene: HSCB as Amber List (moderate evidence)
Mendeliome v0.9196 HSCB Zornitza Stark Gene: hscb has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9195 HSCB Zornitza Stark gene: HSCB was added
gene: HSCB was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: HSCB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HSCB were set to 32634119
Phenotypes for gene: HSCB were set to Anaemia, sideroblastic, 5, MIM# 619523
Review for gene: HSCB was set to AMBER
Added comment: Single individual reported with compound heterozygous variants in this gene. Good functional data including animal model.
Sources: Expert list
Red cell disorders v1.2 HSCB Zornitza Stark Marked gene: HSCB as ready
Red cell disorders v1.2 HSCB Zornitza Stark Gene: hscb has been classified as Amber List (Moderate Evidence).
Red cell disorders v1.2 HSCB Zornitza Stark Classified gene: HSCB as Amber List (moderate evidence)
Red cell disorders v1.2 HSCB Zornitza Stark Gene: hscb has been classified as Amber List (Moderate Evidence).
Red cell disorders v1.1 HSCB Zornitza Stark gene: HSCB was added
gene: HSCB was added to Red cell disorders. Sources: Expert list
Mode of inheritance for gene: HSCB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HSCB were set to 32634119
Phenotypes for gene: HSCB were set to Anaemia, sideroblastic, 5 619523
Review for gene: HSCB was set to AMBER
Added comment: Single individual reported with compound heterozygous variants in this gene. Good functional data including animal model.
Sources: Expert list
Mendeliome v0.9194 FAM57B Zornitza Stark Phenotypes for gene: FAM57B were changed from Cone–rod dystrophy; Maculopathy to Cone-rod dystrophy 22, MIM# 619531; Maculopathy
Mendeliome v0.9193 FAM57B Zornitza Stark edited their review of gene: FAM57B: Changed phenotypes: Cone-rod dystrophy 22, MIM# 619531, Maculopathy
Cone-rod Dystrophy v0.31 FAM57B Zornitza Stark Marked gene: FAM57B as ready
Cone-rod Dystrophy v0.31 FAM57B Zornitza Stark Gene: fam57b has been classified as Green List (High Evidence).
Cone-rod Dystrophy v0.31 FAM57B Zornitza Stark Classified gene: FAM57B as Green List (high evidence)
Cone-rod Dystrophy v0.31 FAM57B Zornitza Stark Gene: fam57b has been classified as Green List (High Evidence).
Cone-rod Dystrophy v0.30 FAM57B Zornitza Stark gene: FAM57B was added
gene: FAM57B was added to Cone-rod Dystrophy. Sources: Expert Review
new gene name tags were added to gene: FAM57B.
Mode of inheritance for gene: FAM57B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM57B were set to 33077892
Phenotypes for gene: FAM57B were set to Cone-rod dystrophy 22, MIM# 619531; Maculopathy
Review for gene: FAM57B was set to GREEN
Added comment: 4 patients with cone-rod dystrophy or maculopathy from 3 families, with LOF pathogenic variants in TLCD3B (ceramide synthase gene). Ceramide is a proapoptotic lipid as high levels of ceramides can lead to apoptosis of neuronal cells, including photoreceptors. Variants segregated with disease. TLCD3B showed high expression in the adult retina with higher expression in the macular than in the peripheral region. Tlcd3bKO/KO mice exhibited a significant reduction of the cone photoreceptor light responses, thinning of the outer nuclear layer, and loss of cone photoreceptors across the retina.
Sources: Expert Review
Retinitis pigmentosa v0.101 FAM57B Zornitza Stark Phenotypes for gene: FAM57B were changed from Cone–rod dystrophy; Maculopathy to Cone-rod dystrophy 22, MIM# 619531; Maculopathy
Retinitis pigmentosa v0.100 FAM57B Zornitza Stark reviewed gene: FAM57B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cone-rod dystrophy 22, MIM# 619531; Mode of inheritance: None
Mendeliome v0.9193 CADM3 Zornitza Stark Phenotypes for gene: CADM3 were changed from Charcot-Marie-Tooth disease to Charcot-Marie-Tooth disease, axonal, type 2FF, MIM# 619519
Mendeliome v0.9192 CADM3 Zornitza Stark reviewed gene: CADM3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2FF, MIM# 619519; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v0.99 CAMTA1 Zornitza Stark changed review comment from: Combination of ID with ataxia overlaps with CP.
Sources: Expert list; to: Combination of ID with ataxia overlaps with CP. At least 3 families reported, intragenic deletions.
Sources: Expert list
Cerebral Palsy v0.99 CAMTA1 Zornitza Stark Marked gene: CAMTA1 as ready
Cerebral Palsy v0.99 CAMTA1 Zornitza Stark Gene: camta1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.99 CAMTA1 Zornitza Stark Tag SV/CNV tag was added to gene: CAMTA1.
Cerebral Palsy v0.99 CAMTA1 Zornitza Stark Classified gene: CAMTA1 as Green List (high evidence)
Cerebral Palsy v0.99 CAMTA1 Zornitza Stark Gene: camta1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.98 CAMTA1 Zornitza Stark gene: CAMTA1 was added
gene: CAMTA1 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: CAMTA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAMTA1 were set to 22693284; 24738973
Phenotypes for gene: CAMTA1 were set to Cerebellar ataxia, nonprogressive, with mental retardation, MIM# 614756
Review for gene: CAMTA1 was set to GREEN
Added comment: Combination of ID with ataxia overlaps with CP.
Sources: Expert list
Cerebral Palsy v0.97 CACNA1A Zornitza Stark Marked gene: CACNA1A as ready
Cerebral Palsy v0.97 CACNA1A Zornitza Stark Gene: cacna1a has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v0.97 CACNA1A Zornitza Stark Classified gene: CACNA1A as Amber List (moderate evidence)
Cerebral Palsy v0.97 CACNA1A Zornitza Stark Gene: cacna1a has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v0.96 CACNA1A Zornitza Stark gene: CACNA1A was added
gene: CACNA1A was added to Cerebral Palsy. Sources: Expert Review
Mode of inheritance for gene: CACNA1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CACNA1A were set to 29761117
Phenotypes for gene: CACNA1A were set to Developemental and epileptic encephalopathy 42, MIM# 617106; Episodic ataxia, type 2, MIM# 108500; Migraine, familial hemiplegic, 1, MIM# 141500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia 141500; Spinocerebellar ataxia 6, MIM# 183086
Review for gene: CACNA1A was set to AMBER
Added comment: Variants in this gene cause a range of phenotypes, including hemiplegia, although this tends to be episodic. Reported in a CP cohort.
Sources: Expert Review
Cerebral Palsy v0.95 BCL11A Zornitza Stark Marked gene: BCL11A as ready
Cerebral Palsy v0.95 BCL11A Zornitza Stark Gene: bcl11a has been classified as Red List (Low Evidence).
Cerebral Palsy v0.95 BCL11A Zornitza Stark gene: BCL11A was added
gene: BCL11A was added to Cerebral Palsy. Sources: Expert Review
Mode of inheritance for gene: BCL11A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: BCL11A were set to Dias-Logan syndrome, MIM# 617101
Review for gene: BCL11A was set to RED
Added comment: Intellectual disability, microcephaly, dysmorphic features and persistence of fetal haemoglobin but no specific overlap with CP.
Sources: Expert Review
Mackenzie's Mission_Reproductive Carrier Screening v0.103 BCAP31 Zornitza Stark gene: BCAP31 was added
gene: BCAP31 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review
Mode of inheritance for gene: BCAP31 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: BCAP31 were set to 24011989; 31330203; 33603160
Phenotypes for gene: BCAP31 were set to Deafness, dystonia, and cerebral hypomyelination, MIM# 300475
Review for gene: BCAP31 was set to GREEN
Added comment: More than 20 unrelated families reported. Clinical features include severe intellectual disability (ID), dystonia, deafness, and central hypomyelination. Female carriers are mostly asymptomatic but may present with deafness.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.4129 BCAP31 Zornitza Stark Marked gene: BCAP31 as ready
Intellectual disability syndromic and non-syndromic v0.4129 BCAP31 Zornitza Stark Gene: bcap31 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4129 BCAP31 Zornitza Stark Phenotypes for gene: BCAP31 were changed from to Deafness, dystonia, and cerebral hypomyelination, MIM# 300475
Intellectual disability syndromic and non-syndromic v0.4128 BCAP31 Zornitza Stark Publications for gene: BCAP31 were set to
Intellectual disability syndromic and non-syndromic v0.4127 BCAP31 Zornitza Stark Mode of inheritance for gene: BCAP31 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.4126 BCAP31 Zornitza Stark reviewed gene: BCAP31: Rating: GREEN; Mode of pathogenicity: None; Publications: 24011989, 31330203, 33603160; Phenotypes: Deafness, dystonia, and cerebral hypomyelination, MIM# 300475; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.9192 BCAP31 Zornitza Stark Marked gene: BCAP31 as ready
Mendeliome v0.9192 BCAP31 Zornitza Stark Gene: bcap31 has been classified as Green List (High Evidence).
Mendeliome v0.9192 BCAP31 Zornitza Stark Phenotypes for gene: BCAP31 were changed from to Deafness, dystonia, and cerebral hypomyelination, MIM# 300475
Mendeliome v0.9191 BCAP31 Zornitza Stark Publications for gene: BCAP31 were set to
Mendeliome v0.9190 BCAP31 Zornitza Stark Mode of inheritance for gene: BCAP31 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.9189 BCAP31 Zornitza Stark reviewed gene: BCAP31: Rating: GREEN; Mode of pathogenicity: None; Publications: 24011989, 31330203, 33603160; Phenotypes: Deafness, dystonia, and cerebral hypomyelination, MIM# 300475; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebral Palsy v0.94 BCAP31 Zornitza Stark Marked gene: BCAP31 as ready
Cerebral Palsy v0.94 BCAP31 Zornitza Stark Gene: bcap31 has been classified as Green List (High Evidence).
Cerebral Palsy v0.94 BCAP31 Zornitza Stark Classified gene: BCAP31 as Green List (high evidence)
Cerebral Palsy v0.94 BCAP31 Zornitza Stark Gene: bcap31 has been classified as Green List (High Evidence).
Cerebral Palsy v0.93 BCAP31 Zornitza Stark gene: BCAP31 was added
gene: BCAP31 was added to Cerebral Palsy. Sources: Expert Review
Mode of inheritance for gene: BCAP31 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: BCAP31 were set to 24011989; 31330203
Phenotypes for gene: BCAP31 were set to Deafness, dystonia, and cerebral hypomyelination, MIM# 300475
Review for gene: BCAP31 was set to GREEN
Added comment: Phenotypic overlap with CP due to combination of almost no psychomotor development with dystonia and pyramidal signs. At least one patient reported who specifically had a CP diagnosis.
Sources: Expert Review
Cerebral Palsy v0.91 AUTS2 Zornitza Stark Marked gene: AUTS2 as ready
Cerebral Palsy v0.91 AUTS2 Zornitza Stark Gene: auts2 has been classified as Green List (High Evidence).
Cerebral Palsy v0.91 AUTS2 Zornitza Stark Classified gene: AUTS2 as Green List (high evidence)
Cerebral Palsy v0.91 AUTS2 Zornitza Stark Gene: auts2 has been classified as Green List (High Evidence).
Cerebral Palsy v0.90 AUTS2 Zornitza Stark gene: AUTS2 was added
gene: AUTS2 was added to Cerebral Palsy. Sources: Expert list
SV/CNV tags were added to gene: AUTS2.
Mode of inheritance for gene: AUTS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AUTS2 were set to 23332918; 27075013
Phenotypes for gene: AUTS2 were set to Mental retardation, autosomal dominant 26, MIM# 615834
Review for gene: AUTS2 was set to GREEN
Added comment: Multiple individuals reported with ID/autism, but 'cerebral palsy' was the original clinical diagnosis in some.

Predominantly deletions reported, so may not be tractable by all NGS assays.
Sources: Expert list
Pulmonary Fibrosis_Interstitial Lung Disease v0.33 AFF4 Zornitza Stark Marked gene: AFF4 as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.33 AFF4 Zornitza Stark Gene: aff4 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.33 AFF4 Zornitza Stark Classified gene: AFF4 as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.33 AFF4 Zornitza Stark Gene: aff4 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.32 AFF4 Zornitza Stark gene: AFF4 was added
gene: AFF4 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Expert Review
Mode of inheritance for gene: AFF4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AFF4 were set to 31058441; 25730767
Phenotypes for gene: AFF4 were set to CHOPS syndrome, MIM# 616368
Review for gene: AFF4 was set to GREEN
Added comment: Chronic interstitial lung disease is a feature of this condition. More than 15 unrelated individuals reported.
Sources: Expert Review
Cerebral Palsy v0.89 ATRX Zornitza Stark Marked gene: ATRX as ready
Cerebral Palsy v0.89 ATRX Zornitza Stark Gene: atrx has been classified as Green List (High Evidence).
Cerebral Palsy v0.89 ATRX Zornitza Stark Classified gene: ATRX as Green List (high evidence)
Cerebral Palsy v0.89 ATRX Zornitza Stark Gene: atrx has been classified as Green List (High Evidence).
Cerebral Palsy v0.88 ATRX Zornitza Stark gene: ATRX was added
gene: ATRX was added to Cerebral Palsy. Sources: Expert Review
Mode of inheritance for gene: ATRX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: ATRX were set to Alpha-thalassemia/mental retardation syndrome, MIM# 301040; Mental retardation-hypotonic facies syndrome, X-linked, MIM# 309580
Review for gene: ATRX was set to GREEN
Added comment: ID and hypotonia/hypertonia/spasticity: phenotypic overlap with CP. Well established gene-disease association.
Sources: Expert Review
Cerebral Palsy v0.87 ATP1A3 Zornitza Stark Marked gene: ATP1A3 as ready
Cerebral Palsy v0.87 ATP1A3 Zornitza Stark Gene: atp1a3 has been classified as Red List (Low Evidence).
Cerebral Palsy v0.87 ATP1A3 Zornitza Stark edited their review of gene: ATP1A3: Changed rating: RED
Cerebral Palsy v0.87 ATP1A3 Zornitza Stark Classified gene: ATP1A3 as Red List (low evidence)
Cerebral Palsy v0.87 ATP1A3 Zornitza Stark Gene: atp1a3 has been classified as Red List (Low Evidence).
Cerebral Palsy v0.86 ATP1A3 Zornitza Stark gene: ATP1A3 was added
gene: ATP1A3 was added to Cerebral Palsy. Sources: Expert Review
Mode of inheritance for gene: ATP1A3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ATP1A3 were set to Alternating hemiplegia of childhood 2, MIM# 614820; CAPOS syndrome, MIM# 601338; Dystonia-12, MIM# 128235
Review for gene: ATP1A3 was set to GREEN
Added comment: The disorders associated with variants in this gene tend to have episodic symptoms, insufficient overlap with CP.
Sources: Expert Review
Cerebral Palsy v0.85 ASXL3 Zornitza Stark Marked gene: ASXL3 as ready
Cerebral Palsy v0.85 ASXL3 Zornitza Stark Gene: asxl3 has been classified as Red List (Low Evidence).
Cerebral Palsy v0.85 ASXL3 Zornitza Stark gene: ASXL3 was added
gene: ASXL3 was added to Cerebral Palsy. Sources: Expert Review
Mode of inheritance for gene: ASXL3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ASXL3 were set to Bainbridge-Ropers syndrome, MIM# 615485
Review for gene: ASXL3 was set to RED
Added comment: Severe neurodevelopmental disorder but no strong overlap with CP.
Sources: Expert Review
Cerebral Palsy v0.84 ARX Zornitza Stark Marked gene: ARX as ready
Cerebral Palsy v0.84 ARX Zornitza Stark Gene: arx has been classified as Green List (High Evidence).
Cerebral Palsy v0.84 ARX Zornitza Stark Classified gene: ARX as Green List (high evidence)
Cerebral Palsy v0.84 ARX Zornitza Stark Gene: arx has been classified as Green List (High Evidence).
Cerebral Palsy v0.83 ARX Zornitza Stark gene: ARX was added
gene: ARX was added to Cerebral Palsy. Sources: Expert Review
Mode of inheritance for gene: ARX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: ARX were set to Developmental and epileptic encephalopathy 1, MIM# 308350; Lissencephaly, X-linked 2, MIM# 300215; Proud syndrome, MIM# 300004
Review for gene: ARX was set to GREEN
Added comment: Well established gene-disease association. Phenotypic overlap: ID/seizures/abnormal tone.
Sources: Expert Review
Cerebral Palsy v0.82 AMPD2 Zornitza Stark Marked gene: AMPD2 as ready
Cerebral Palsy v0.82 AMPD2 Zornitza Stark Gene: ampd2 has been classified as Green List (High Evidence).
Cerebral Palsy v0.82 AMPD2 Zornitza Stark Classified gene: AMPD2 as Green List (high evidence)
Cerebral Palsy v0.82 AMPD2 Zornitza Stark Gene: ampd2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4126 AMPD2 Zornitza Stark Marked gene: AMPD2 as ready
Intellectual disability syndromic and non-syndromic v0.4126 AMPD2 Zornitza Stark Gene: ampd2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4126 AMPD2 Zornitza Stark Phenotypes for gene: AMPD2 were changed from to Pontocerebellar hypoplasia, type 9, MIM#615809
Intellectual disability syndromic and non-syndromic v0.4125 AMPD2 Zornitza Stark Publications for gene: AMPD2 were set to
Intellectual disability syndromic and non-syndromic v0.4124 AMPD2 Zornitza Stark Mode of inheritance for gene: AMPD2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4123 AMPD2 Zornitza Stark reviewed gene: AMPD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23911318, 27066553; Phenotypes: Pontocerebellar hypoplasia, type 9, MIM#615809; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9189 AMPD2 Zornitza Stark Marked gene: AMPD2 as ready
Mendeliome v0.9189 AMPD2 Zornitza Stark Gene: ampd2 has been classified as Green List (High Evidence).
Mendeliome v0.9189 AMPD2 Zornitza Stark Phenotypes for gene: AMPD2 were changed from to Pontocerebellar hypoplasia, type 9, MIM#615809
Mendeliome v0.9188 AMPD2 Zornitza Stark Publications for gene: AMPD2 were set to
Mendeliome v0.9187 AMPD2 Zornitza Stark Mode of inheritance for gene: AMPD2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9186 AMPD2 Zornitza Stark Deleted their comment
Mendeliome v0.9186 AMPD2 Zornitza Stark edited their review of gene: AMPD2: Added comment: Well established gene-disease association. Clinical features include severely delayed psychomotor development, progressive microcephaly, spasticity, seizures, and brain abnormalities, including brain atrophy, thin corpus callosum, and delayed myelination.; Changed rating: GREEN; Changed publications: 23911318, 27066553
Cerebral Palsy v0.81 AMPD2 Zornitza Stark gene: AMPD2 was added
gene: AMPD2 was added to Cerebral Palsy. Sources: Expert Review
Mode of inheritance for gene: AMPD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AMPD2 were set to 23911318; 27066553; 29761117
Phenotypes for gene: AMPD2 were set to Pontocerebellar hypoplasia, type 9, MIM# 615809
Review for gene: AMPD2 was set to GREEN
Added comment: Well established gene-disease association. Phenotypic overlap: ID and spastic paraplegia. Reported in CP cohort.
Sources: Expert Review
Incidentalome v0.79 Zornitza Stark removed gene:ALS2 from the panel
Mendeliome v0.9186 ALS2 Zornitza Stark Marked gene: ALS2 as ready
Mendeliome v0.9186 ALS2 Zornitza Stark Gene: als2 has been classified as Green List (High Evidence).
Mendeliome v0.9186 ALS2 Zornitza Stark Classified gene: ALS2 as Green List (high evidence)
Mendeliome v0.9186 ALS2 Zornitza Stark Gene: als2 has been classified as Green List (High Evidence).
Cerebral Palsy v0.80 ALS2 Zornitza Stark Marked gene: ALS2 as ready
Cerebral Palsy v0.80 ALS2 Zornitza Stark Gene: als2 has been classified as Green List (High Evidence).
Cerebral Palsy v0.80 ALS2 Zornitza Stark Classified gene: ALS2 as Green List (high evidence)
Cerebral Palsy v0.80 ALS2 Zornitza Stark Gene: als2 has been classified as Green List (High Evidence).
Cerebral Palsy v0.79 ALS2 Zornitza Stark gene: ALS2 was added
gene: ALS2 was added to Cerebral Palsy. Sources: Expert Review
Mode of inheritance for gene: ALS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALS2 were set to 12145748; 33409823; 30128655
Phenotypes for gene: ALS2 were set to Spastic paralysis, infantile onset ascending, MIM# 607225
Review for gene: ALS2 was set to GREEN
Added comment: Well established gene-disease association. Phenotypic overlap with CP.
Sources: Expert Review
Cerebral Palsy v0.78 ALDH3A2 Zornitza Stark Marked gene: ALDH3A2 as ready
Cerebral Palsy v0.78 ALDH3A2 Zornitza Stark Gene: aldh3a2 has been classified as Green List (High Evidence).
Cerebral Palsy v0.78 ALDH3A2 Zornitza Stark Classified gene: ALDH3A2 as Green List (high evidence)
Cerebral Palsy v0.78 ALDH3A2 Zornitza Stark Gene: aldh3a2 has been classified as Green List (High Evidence).
Cerebral Palsy v0.77 ALDH3A2 Zornitza Stark gene: ALDH3A2 was added
gene: ALDH3A2 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: ALDH3A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALDH3A2 were set to 9027499; 9829906; 28543186
Phenotypes for gene: ALDH3A2 were set to Sjogren-Larsson syndrome, MIM# 270200
Review for gene: ALDH3A2 was set to GREEN
Added comment: Well established gene-disease association. Phenotypic overlap with CP: ID and spastic paraplegia.
Sources: Expert list
Red cell disorders v1.0 Zornitza Stark promoted panel to version 1.0
Red cell disorders v0.222 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Mendeliome v0.9185 HBG2 Zornitza Stark Marked gene: HBG2 as ready
Mendeliome v0.9185 HBG2 Zornitza Stark Gene: hbg2 has been classified as Green List (High Evidence).
Mendeliome v0.9185 HBG2 Zornitza Stark Phenotypes for gene: HBG2 were changed from to Fetal hemoglobin quantitative trait locus 1, MIM# 141749; Cyanosis, transient neonatal, MIM# 613977
Mendeliome v0.9184 HBG2 Zornitza Stark Publications for gene: HBG2 were set to
Mendeliome v0.9183 HBG2 Zornitza Stark Mode of inheritance for gene: HBG2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9182 HBG2 Zornitza Stark reviewed gene: HBG2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26500940; Phenotypes: Fetal hemoglobin quantitative trait locus 1, MIM# 141749, Cyanosis, transient neonatal, MIM# 613977; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Red cell disorders v0.221 HBG2 Zornitza Stark Marked gene: HBG2 as ready
Red cell disorders v0.221 HBG2 Zornitza Stark Gene: hbg2 has been classified as Green List (High Evidence).
Red cell disorders v0.221 HBG2 Zornitza Stark Phenotypes for gene: HBG2 were changed from Cyanosis, transient neonatal, 613977; 141749 Globin Disorder; Globin Disorder; Fetal hemoglobin quantitative trait locus 1; 141749 Hereditary persistance of fetal haemoglobin; Fetal hemoglobin quantitative trait locus 1,141749 to Fetal haemoglobin quantitative trait locus 1, MIM# 141749; Cyanosis, transient neonatal, MIM# 613977
Red cell disorders v0.220 HBG2 Zornitza Stark Mode of inheritance for gene: HBG2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Red cell disorders v0.219 HBG2 Zornitza Stark reviewed gene: HBG2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fetal hemoglobin quantitative trait locus 1, MIM# 141749, Cyanosis, transient neonatal, MIM# 613977; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9182 HBG1 Zornitza Stark Marked gene: HBG1 as ready
Mendeliome v0.9182 HBG1 Zornitza Stark Gene: hbg1 has been classified as Green List (High Evidence).
Mendeliome v0.9182 HBG1 Zornitza Stark Classified gene: HBG1 as Green List (high evidence)
Mendeliome v0.9182 HBG1 Zornitza Stark Gene: hbg1 has been classified as Green List (High Evidence).
Mendeliome v0.9181 HBG1 Zornitza Stark gene: HBG1 was added
gene: HBG1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: HBG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HBG1 were set to 26500940
Phenotypes for gene: HBG1 were set to Fetal haemoglobin quantitative trait locus 1, 141749
Review for gene: HBG1 was set to GREEN
Added comment: Classic hereditary persistence of fetal hemoglobin (HPFH) is characterized by a substantial elevation of fetal hemoglobin (HbF) in adult red blood cells. There are no other phenotypic or haematologic manifestations.
Sources: Expert Review
Red cell disorders v0.219 HBG1 Zornitza Stark Marked gene: HBG1 as ready
Red cell disorders v0.219 HBG1 Zornitza Stark Gene: hbg1 has been classified as Green List (High Evidence).
Red cell disorders v0.219 HBG1 Zornitza Stark Phenotypes for gene: HBG1 were changed from 141749 Globin Disorder; Globin Disorder; Fetal hemoglobin quantitative trait locus 1; 141749 Hereditary persistance of fetal haemoglobin; Fetal hemoglobin quantitative trait locus 1, 141749 to Fetal haemoglobin quantitative trait locus 1, 141749
Red cell disorders v0.218 HBG1 Zornitza Stark changed review comment from: Classic hereditary persistence of fetal hemoglobin (HPFH) is characterized by a substantial elevation of fetal hemoglobin (HbF) in adult red blood cells. There are no other phenotypic or hematologic manifestations.; to: Classic hereditary persistence of fetal hemoglobin (HPFH) is characterized by a substantial elevation of fetal hemoglobin (HbF) in adult red blood cells. There are no other phenotypic or haematologic manifestations.
Red cell disorders v0.218 HBG1 Zornitza Stark reviewed gene: HBG1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fetal haemoglobin quantitative trait locus 1 141749; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Red cell disorders v0.218 RPS24 Zornitza Stark Marked gene: RPS24 as ready
Red cell disorders v0.218 RPS24 Zornitza Stark Gene: rps24 has been classified as Green List (High Evidence).
Red cell disorders v0.218 RPS24 Zornitza Stark Phenotypes for gene: RPS24 were changed from Inherited Bone Marrow Failure Syndromes; Diamond-blackfan anemia 3, 610629; Diamond-Blackfan Anemia 3; Diamond Blackfan anemia; Diamond-Blackfan Anemia; DIAMOND-BLACKFAN ANEMIA 3; Diamond_Blackfan Anemia 3; 610629 Diamond_Blackfan Anemia 3; 610629 Diamond-blackfan anemia 3 to Diamond-Blackfan anaemia 3, MIM# 610629
Red cell disorders v0.217 RPS24 Zornitza Stark Publications for gene: RPS24 were set to 17186470; 23812780
Red cell disorders v0.216 RPS19 Zornitza Stark Marked gene: RPS19 as ready
Red cell disorders v0.216 RPS19 Zornitza Stark Gene: rps19 has been classified as Green List (High Evidence).
Red cell disorders v0.216 RPS19 Zornitza Stark Phenotypes for gene: RPS19 were changed from Inherited Bone Marrow Failure Syndromes; Diamond Blackfan anemia; 105650 Diamond-Blackfan anemia 1; 105650 Diamond_Blackfan Anemia 1; Diamond-Blackfan Anemia; DIAMOND-BLACKFAN ANEMIA 1; Diamond-Blackfan anemia 1, 105650; Diamond_Blackfan Anemia to Diamond-Blackfan anaemia 1, MIM# 105650; MONDO:0007110
Red cell disorders v0.215 RPS19 Zornitza Stark Publications for gene: RPS19 were set to 9988267
Red cell disorders v0.214 RPS17 Zornitza Stark Marked gene: RPS17 as ready
Red cell disorders v0.214 RPS17 Zornitza Stark Gene: rps17 has been classified as Green List (High Evidence).
Red cell disorders v0.214 RPS17 Zornitza Stark Phenotypes for gene: RPS17 were changed from Diamond-Blackfan anemia 4, 612527; 612527 Diamond-Blackfan anemia 4 to Diamond-Blackfan anaemia 4, MIM# 612527
Red cell disorders v0.213 RPS10 Zornitza Stark Marked gene: RPS10 as ready
Red cell disorders v0.213 RPS10 Zornitza Stark Gene: rps10 has been classified as Green List (High Evidence).
Red cell disorders v0.213 RPS10 Zornitza Stark Phenotypes for gene: RPS10 were changed from 613308 Diamond-Blackfan anemia 9; Inherited Bone Marrow Failure Syndromes; Diamond Blackfan anemia; DIAMOND-BLACKFAN ANEMIA 9; Diamond-Blackfan Anemia 9; Diamond-Blackfan Anemia; Diamond-Blackfan anemia 9, 613308; 613308 Diamond_Blackfan Anemia 9; Diamond_Blackfan Anemia 9 to Diamond-Blackfan anaemia 9, MIM# 613308
Red cell disorders v0.212 RPS10 Zornitza Stark Publications for gene: RPS10 were set to 20116044
Red cell disorders v0.211 RPL9 Zornitza Stark Marked gene: RPL9 as ready
Red cell disorders v0.211 RPL9 Zornitza Stark Gene: rpl9 has been classified as Amber List (Moderate Evidence).
Red cell disorders v0.211 RPL9 Zornitza Stark Phenotypes for gene: RPL9 were changed from Diamond-Blackfan anemia; N/A Diamond-Blackfan anemia; ?Diamond-Blackfan anaemia to Diamond Blackfan anaemia
Red cell disorders v0.210 RPL9 Zornitza Stark Publications for gene: RPL9 were set to 29114930
Red cell disorders v0.209 RPL9 Zornitza Stark Classified gene: RPL9 as Amber List (moderate evidence)
Red cell disorders v0.209 RPL9 Zornitza Stark Gene: rpl9 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9180 WNT9B Zornitza Stark Marked gene: WNT9B as ready
Mendeliome v0.9180 WNT9B Zornitza Stark Gene: wnt9b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9180 WNT9B Zornitza Stark Phenotypes for gene: WNT9B were changed from to Renal agenesis/hypoplasia/dysplasia
Mendeliome v0.9179 WNT9B Zornitza Stark Publications for gene: WNT9B were set to
Mendeliome v0.9178 WNT9B Zornitza Stark Mode of inheritance for gene: WNT9B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9177 WNT9B Zornitza Stark Classified gene: WNT9B as Amber List (moderate evidence)
Mendeliome v0.9177 WNT9B Zornitza Stark Gene: wnt9b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9176 WNT9B Zornitza Stark reviewed gene: WNT9B: Rating: AMBER; Mode of pathogenicity: None; Publications: 34145744; Phenotypes: Renal agenesis/hypoplasia/dysplasia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9176 DDX23 Zornitza Stark Marked gene: DDX23 as ready
Mendeliome v0.9176 DDX23 Zornitza Stark Gene: ddx23 has been classified as Green List (High Evidence).
Mendeliome v0.9176 DDX23 Zornitza Stark Phenotypes for gene: DDX23 were changed from Developmental disorder to DDX23-associated neurodevelopmental disorder
Mendeliome v0.9175 DDX23 Zornitza Stark Publications for gene: DDX23 were set to 33057194
Mendeliome v0.9174 DDX23 Zornitza Stark Classified gene: DDX23 as Green List (high evidence)
Mendeliome v0.9174 DDX23 Zornitza Stark Gene: ddx23 has been classified as Green List (High Evidence).
Mendeliome v0.9173 DDX23 Zornitza Stark reviewed gene: DDX23: Rating: GREEN; Mode of pathogenicity: None; Publications: 34050707; Phenotypes: DDX23-associated neurodevelopmental disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4123 DDX23 Zornitza Stark Phenotypes for gene: DDX23 were changed from Developmental disorder to DDX23-associated neurodevelopmental disorder
Intellectual disability syndromic and non-syndromic v0.4122 DDX23 Zornitza Stark Publications for gene: DDX23 were set to 33057194
Pituitary hormone deficiency v0.17 CHD7 Belinda Chong edited their review of gene: CHD7: Changed publications: PMID: 29152903, PMID: 30733481
Pituitary hormone deficiency v0.17 CHD7 Belinda Chong reviewed gene: CHD7: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29152903, 30733481; Phenotypes: CHARGE syndrome MIM# 214800, Hypogonadotropic hypogonadism 5 with or without anosmia MIM# 612370; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9173 TAF2 Zornitza Stark Publications for gene: TAF2 were set to 21937992; 22633631; 26350204; 24084144
Mendeliome v0.9172 TAF2 Zornitza Stark Classified gene: TAF2 as Green List (high evidence)
Mendeliome v0.9172 TAF2 Zornitza Stark Gene: taf2 has been classified as Green List (High Evidence).
Mendeliome v0.9171 TAF2 Zornitza Stark edited their review of gene: TAF2: Added comment: New report of 4 individuals from 2 unrelated families, with severe intellectual disability, global developmental delay, postnatal microcephaly, feet deformities and thin corpus callosum. They had homozygous TAF2 missense variants detected by Exome Sequencing.; Changed rating: GREEN; Changed publications: 21937992, 22633631, 26350204, 24084144, 34474177
Microcephaly v1.52 TAF2 Zornitza Stark Publications for gene: TAF2 were set to 21937992; 22633631; 26350204
Intellectual disability syndromic and non-syndromic v0.4121 TAF2 Zornitza Stark Publications for gene: TAF2 were set to 21937992; 22633631; 26350204
Mendeliome v0.9171 ERGIC1 Zornitza Stark Marked gene: ERGIC1 as ready
Mendeliome v0.9171 ERGIC1 Zornitza Stark Gene: ergic1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9171 ERGIC1 Zornitza Stark Classified gene: ERGIC1 as Amber List (moderate evidence)
Mendeliome v0.9171 ERGIC1 Zornitza Stark Gene: ergic1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9170 ERGIC1 Zornitza Stark gene: ERGIC1 was added
gene: ERGIC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ERGIC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERGIC1 were set to 28317099; 34037256
Phenotypes for gene: ERGIC1 were set to Arthrogryposis multiplex congenita 2, neurogenic type; OMIM # 208100
Review for gene: ERGIC1 was set to AMBER
Added comment: Reinstein et al. (2018) used WES in a large consanguineous Israeli Arab kindred consisting of 16 patients affected with the neurogenic type of arthrogryposis multiplex congenita. They identified a homozygous missense (V98E) mutation in ERGIC1 gene, which segregated with the disorder in the kindred, and was not found in the ExAC database or in 212 ethnically matched controls. Functional studies of the variant and studies of patient cells were not performed. ERGIC1 encodes a cycling membrane protein which has a possible role in transport between endoplasmic reticulum and Golgi.

Marconi et al (2021) used genome sequencing in a consanguineous family with 2 affected siblings presenting congenital arthrogryposis and some facial dysmorphism. They identified a homozygous 22.6 Kb deletion encompassing the promoter and first exon of ERGIC1. mRNA quantification showed the complete absence of ERGIC1 expression in the two affected siblings and a decrease in heterozygous parents.
Sources: Literature
Arthrogryposis v0.296 ERGIC1 Zornitza Stark Marked gene: ERGIC1 as ready
Arthrogryposis v0.296 ERGIC1 Zornitza Stark Gene: ergic1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9169 HMGB1 Zornitza Stark Phenotypes for gene: HMGB1 were changed from Mirror image foot polydactyly to Mirror image foot polydactyly; Developmental delay and microcephaly, no OMIM #
Mendeliome v0.9168 HMGB1 Zornitza Stark Publications for gene: HMGB1 were set to 34159400
Intellectual disability syndromic and non-syndromic v0.4120 HMGB1 Zornitza Stark Marked gene: HMGB1 as ready
Intellectual disability syndromic and non-syndromic v0.4120 HMGB1 Zornitza Stark Gene: hmgb1 has been classified as Green List (High Evidence).
Microcephaly v1.51 HMGB1 Zornitza Stark Marked gene: HMGB1 as ready
Microcephaly v1.51 HMGB1 Zornitza Stark Gene: hmgb1 has been classified as Green List (High Evidence).
Imprinting disorders v0.3 SGCE Anna Le Fevre reviewed gene: SGCE: Rating: GREEN; Mode of pathogenicity: None; Publications: 11528394, 12325078, 17200151, 16227522, 20301587, 33200041; Phenotypes: myoclonus, dystonia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Mendeliome v0.9167 HMGB1 Chirag Patel reviewed gene: HMGB1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34164801; Phenotypes: Developmental delay and microcephaly, no OMIM #; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9167 HMGB1 Chirag Patel Classified gene: HMGB1 as Green List (high evidence)
Mendeliome v0.9167 HMGB1 Chirag Patel Gene: hmgb1 has been classified as Green List (High Evidence).
Microcephaly v1.51 HMGB1 Chirag Patel Phenotypes for gene: HMGB1 were changed from Developmental delay and microcephaly, no OMIM # to Developmental delay and microcephaly, no OMIM #
Microcephaly v1.51 HMGB1 Chirag Patel Phenotypes for gene: HMGB1 were changed from 0 ALDH5A1 1 ALDH7A1 0 ALG1 0 ALG11 1 ALG12 1 ALG13 1 ALG14 1 ALG3 1 ALG6 1 ALG8 1 ALG9 1 ALKBH8 1 ALMS1 0 AMER1 0 AMPD2 0 AMT 0 ANK2 2 ANKRD11 0 ANKRD17 2 AP1B1 1 AP1G1 1 AP1S1 0 AP1S2 0 AP2M1 1 AP3B1 0 AP3B2 1 AP4B1 1 AP4E1 1 AP4M1 1 AP4S1 1 APC2 1 APOPT1 1 ARCN1 1 ARF1 1 ARFGEF2 0 ARG1 0 ARHGEF9 1 ARID1A 1 ARID1B 1 ARID2 2 ARL13B 1 ARL6 1 ARMC9 1 ARSA 0 ARSB 1 ARSE 1 ARV1 0 ARX 0 ASAH1 0 ASH1L 1 ASL 1 ASNS 1 ASPA 0 ASPM 1 ASS1 0 ASTN1 1 ASXL1 0 ASXL2 0 ASXL3 1 ATAD1 1 ATAD3A 1 ATG7 1 ATIC 1 ATM 0 ATN1 1 ATP13A2 0 ATP1A1 1 ATP1A2 1 ATP1A3 2 ATP6AP1 1 ATP6AP2 0 ATP6V0A2 0 ATP6V1A 1 ATP6V1B2 0 ATP7A 0 ATP8A2 1 ATR 0 ATRX 0 AUH 0 AUTS2 1 B3GALNT2 1 B3GLCT 0 B4GALNT1 0 B4GALT1 1 B4GALT7 1 B9D2 1 BAZ2B 1 BBS1 0 BBS10 0 BBS12 0 BBS2 0 BBS4 1 BBS5 1 BBS7 1 BBS9 1 BCAP31 0 BCAS3 1 BCKDHA 0 BCKDHB 0 BCKDK 0 BCL11A 0 BCL11B 1 BCOR 1 BCORL1 1 BCS1L 0 BICRA 3 BLM 0 BMP4 0 BOLA3 0 BPTF 1 BRAF 0 BRAT1 1 BRD4 2 BRF1 1 BRIP1 1 BRPF1 1 BRSK2 1 BRWD3 0 BSCL2 0 BSND 1 BTD 0 BUB1B 0 C12orf4 0 C12orf57 0 C12orf65 0 C2CD3 1 C2orf69 1 C5orf42 1 CA2 1 CA8 1 CACNA1A 0 CACNA1B 1 CACNA1C 0 CACNA1D 1 CACNA1E 1 CACNA1G 2 CACNA1I 1 CACNA2D2 1 CAD 1 CAMK2A 0 CAMK2B 1 CAMK4 1 CAMTA1 2 CAPN15 1 CARS 1 CARS2 1 CASK 0 CBL 0 CBS 0 CBY1 1 CC2D1A 1 CC2D2A 0 CCBE1 1 CCDC22 0 CCDC47 1 CCDC88A 1 CCDC88C 2 CCND2 0 CDC42 0 CDC42BPB 1 CDH11 2 CDH15 0 CDH2 1 CDK10 0 CDK13 1 CDK19 1 CDK5RAP2 1 CDK8 1 CDKL5 0 CDON 0 CELF2 1 CENPF 0 CENPJ 0 CEP104 1 CEP120 1 CEP135 1 CEP152 1 CEP164 1 CEP290 0 CEP41 0 CEP55 1 CEP57 1 CEP83 1 CEP85L 1 CHAMP1 0 CHD1 1 CHD2 0 CHD3 1 CHD4 1 CHD5 1 CHD7 0 CHD8 0 CHKB 0 CHMP1A 1 CIC 0 CIT 0 CKAP2L 0 CLCN3 1 CLCN4 1 CLCN6 1 CLCNKB 1 CLN3 0 CLN5 1 CLN6 0 CLN8 0 CLP1 1 CLPB 1 CLTC 1 CNKSR2 0 CNNM2 0 CNOT1 3 CNOT2 1 CNOT3 2 CNPY3 1 CNTNAP1 1 CNTNAP2 0 COASY 1 COG1 0 COG4 1 COG5 1 COG6 1 COG7 0 COG8 1 COL4A1 0 COL4A2 0 COL4A3BP 0 COLEC11 0 COPB2 2 COQ4 0 COQ8A 0 COX10 1 COX15 0 CPS1 0 CRADD 1 CRB2 0 CREBBP 1 CSDE1 1 CSNK1G1 2 CSNK2A1 0 CSNK2B 0 CSPP1 1 CSTB 0 CTBP1 1 CTCF 1 CTDP1 0 CTNNA2 1 CTNNB1 0 CTSA 0 CTSD 0 CTU2 1 CUL3 2 CUL4B 0 CUX1 1 CUX2 1 CWC27 0 CWF19L1 1 CXorf56 1 CYB5R3 0 CYC1 0 CYFIP2 1 D2HGDH 0 DAG1 0 DARS 1 DARS2 0 DBT 0 DCAF17 0 DCHS1 0 DCPS 1 DCX 0 DDB1 2 DDC 0 DDHD2 0 DDX11 1 DDX23 2 DDX3X 0 DDX59 1 DDX6 1 DEAF1 1 DEGS1 1 DENND5A 1 DEPDC5 0 DHCR24 0 DHCR7 0 DHDDS 1 DHFR 1 DHPS 1 DHTKD1 0 DHX30 1 DHX37 2 DIAPH1 0 DIS3L2 0 DKC1 0 DLD 0 DLG3 1 DLG4 2 DLL1 1 DMD 0 DMXL2 1 DNAJC12 1 DNAJC19 0 DNM1 1 DNM1L 1 DNMT3A 1 DNMT3B 0 DOCK3 1 DOCK6 1 DOCK7 1 DOCK8 0 DOLK 1 DPAGT1 1 DPF2 0 DPH1 1 DPM1 0 DPM2 1 DPYD 1 DPYS 1 DPYSL5 1 DYM 1 DYNC1H1 0 DYNC1I2 1 DYRK1A 1 EARS2 1 EBF3 1 EBP 1 EDEM3 2 EED 1 EEF1A2 1 EEF2 1 EFTUD2 1 EHMT1 1 EIF2AK2 2 EIF2AK3 0 EIF2S3 1 EIF3F 1 EIF4A3 1 EIF5A 1 ELAC2 0 ELOVL4 0 ELP2 0 EMC1 1 EMC10 2 EML1 1 EP300 0 EPG5 1 ERCC1 1 ERCC2 0 ERCC3 0 ERCC5 1 ERCC6 0 ERCC6L2 0 ERCC8 0 ERLIN2 1 ESCO2 0 ETFA 1 ETFB 1 ETFDH 1 ETHE1 0 EXOC7 1 EXOSC3 0 EXOSC8 1 EXT2 1 EXTL3 1 EZH2 1 FAM111A 0 FAM126A 0 FAM20C 0 FAM50A 1 FAR1 1 FARS2 1 FARSA 1 FARSB 1 FAT4 0 FBRSL1 1 FBXL3 2 FBXL4 0 FBXO11 1 FBXO28 1 FBXO31 2 FBXW11 2 FBXW7 1 FDFT1 1 FGD1 1 FGF12 0 FGF13 1 FGF14 1 FGFR1 1 FGFR3 1 FH 0 FIG4 0 FITM2 1 FKRP 0 FKTN 0 FLNA 0 FLVCR2 0 FMN2 0 FMR1 0 FOLR1 1 FOXG1 0 FOXP1 2 FOXP2 1 FOXRED1 0 FRAS1 1 FRMPD4 1 FRRS1L 1 FTCD 1 FTSJ1 0 FUCA1 0 FUT8 1 GABBR2 1 GABRA1 1 GABRA2 1 GABRA5 1 GABRB2 0 GABRB3 1 GABRG2 1 GAD1 1 GALC 0 GALE 0 GALNT2 1 GALT 1 GAMT 0 GATA6 1 GATAD2B 1 GATM 1 GCDH 0 GCH1 0 GDI1 0 GEMIN5 1 GFAP 0 GFER 1 GFM1 0 GJC2 0 GK 0 GLB1 0 GLDC 0 GLI2 0 GLI3 0 GLIS3 1 GLS 1 GLUL 0 GLYCTK 0 GM2A 0 GMPPA 0 GMPPB 0 GNAI1 2 GNAO1 1 GNAS 1 GNB1 1 GNB2 3 GNB5 1 GNE 1 GNPAT 0 GNPTAB 0 GNPTG 1 GNS 0 GOLGA2 2 GOT2 1 GPAA1 1 GPC3 0 GPC4 1 GPT2 1 GRIA1 1 GRIA2 2 GRIA3 1 GRIA4 0 GRID2 0 GRIK2 1 GRIN1 1 GRIN2A 1 GRIN2B 1 GRIN2D 1 GRM1 0 GRM7 1 GSS 1 GTF2H5 0 GTF3C3 1 GTPBP2 1 GTPBP3 0 GUSB 1 H3F3A 1 H3F3B 1 HACE1 1 HADHA 0 HADHB 1 HCCS 0 HCFC1 0 HCN1 0 HDAC4 2 HDAC8 1 HECW2 2 HEPACAM 0 HERC1 0 HERC2 2 HESX1 0 HEXA 0 HEXB 0 HGSNAT 1 HIBCH 0 HID1 1 HIRA 1 HIST1H1E 1 HIST1H4C 2 HIVEP2 1 HK1 2 HLCS 0 HMGB1 1 HMGCL 0 HNMT 1 HNRNPH1 1 HNRNPH2 0 HNRNPK 0 HNRNPR 1 HNRNPU 1 HOXA1 0 HPD 0 HPDL 2 HPRT1 0 HRAS 1 HS2ST1 3 HSD17B10 0 HSD17B4 1 HSPD1 0 HSPG2 1 HTRA2 0 HUWE1 1 IARS 1 IBA57 1 IDH2 0 IDS 0 IDUA 0 IER3IP1 1 IFIH1 0 IFT172 0 IFT27 1 IFT74 1 IGF1 1 IGF1R 1 IKBKG 0 IL1RAPL1 0 IMPDH2 2 INPP5E 1 INPP5K 0 INTS1 1 IQSEC1 1 IQSEC2 1 IREB2 1 IRF2BPL 1 ISCA1 1 ISCA2 1 ISPD 0 ITPA 0 ITPR1 0 IVD 0 JAM3 1 JARID2 1 JMJD1C 2 KANSL1 1 KARS 1 KAT5 2 KAT6A 0 KAT6B 0 KAT8 1 KATNB1 1 KCNA2 1 KCNB1 1 KCNC1 0 KCNH1 1 KCNJ10 0 KCNJ11 0 KCNJ6 1 KCNK4 1 KCNK9 1 KCNMA1 1 KCNN2 1 KCNN3 1 KCNQ2 0 KCNQ3 1 KCNQ5 1 KCNT1 0 KCNT2 1 KCTD3 0 KCTD7 0 KDM1A 1 KDM3B 2 KDM4B 2 KDM5B 1 KDM5C 1 KDM6A 0 KDM6B 1 KIAA0586 0 KIAA1109 0 KIDINS220 1 KIF11 2 KIF14 1 KIF1A 2 KIF1BP 1 KIF21B 1 KIF2A 1 KIF5A 0 KIF5C 1 KIF7 0 KLF7 1 KLHL7 0 KMT2A 1 KMT2B 1 KMT2C 1 KMT2D 2 KMT2E 1 KMT5B 1 KNL1 1 KPTN 1 KRAS 0 L1CAM 0 L2HGDH 0 LAMA1 0 LAMA2 1 LAMB1 1 LAMB2 1 LAMC3 0 LAMP2 0 LARGE1 0 LARP7 1 LARS 2 LARS2 0 LIAS 1 LIG4 0 LINGO4 1 LINS1 0 LIPT1 1 LMBRD1 1 LMBRD2 2 LMNB1 2 LMNB2 2 LONP1 0 LRP2 0 LRPPRC 0 LSS 1 LTBP1 1 LYRM7 1 LZTFL1 1 LZTR1 1 MAB21L1 2 MAB21L2 1 MACF1 1 MADD 3 MAF 0 MAGEL2 1 MAN1B1 1 MAN2B1 1 MANBA 1 MAOA 1 MAP1B 1 MAP2K1 0 MAP2K2 0 MAPK1 2 MAPK8IP3 2 MAPKAPK5 1 MAPRE2 1 MASP1 1 MAST1 1 MAST3 1 MAT1A 0 MBD5 1 MBOAT7 0 MBTPS2 0 MCCC1 0 MCCC2 0 MCM3AP 1 MCOLN1 1 MCPH1 1 MDH2 0 MECP2 1 MED12 0 MED12L 1 MED13 1 MED13L 0 MED17 1 MED23 0 MED25 1 MED27 2 MEF2C 1 MEGF8 2 MEIS2 0 METTL23 2 METTL5 1 MFF 0 MFSD2A 1 MFSD8 1 MGAT2 1 MICU1 1 MID1 0 MIR17HG 2 MKKS 0 MKS1 0 MLC1 0 MLYCD 1 MMAA 0 MMAB 0 MMACHC 0 MMADHC 0 MN1 2 MOCS1 1 MOCS2 0 MOGS 1 MORC2 2 MPDU1 1 MPDZ 1 MPLKIP 1 MPP5 1 MPV17 1 MRPS22 0 MRPS34 1 MSL3 1 MSMO1 1 MTFMT 0 MTHFR 0 MTHFS 1 MTO1 1 MTOR 0 MTR 1 MTRR 1 MUT 0 MVK 0 MYCN 0 MYO5A 0 MYT1L 2 NAA10 0 NAA15 1 NACC1 0 NAGA 0 NAGLU 0 NALCN 0 NANS 0 NARS 2 NBEA 1 NCAPD2 2 NCAPG2 1 NCDN 2 NCKAP1 1 NDE1 1 NDP 0 NDST1 0 NDUFA1 0 NDUFA2 1 NDUFAF1 1 NDUFS1 1 NDUFS4 1 NDUFS7 0 NDUFS8 0 NDUFV1 0 NEDD4L 1 NEMF 2 NEU1 0 NEUROD2 1 NEXMIF 1 NF1 0 NFASC 1 NFIA 0 NFIB 1 NFIX 0 NFU1 1 NGLY1 0 NHS 0 NIPBL 1 NKAP 1 NKX2-1 0 NLGN3 0 NONO 0 NOVA2 1 NPC1 0 NPC2 0 NPHP1 0 NPHP3 1 NR2F1 1 NR4A2 2 NRAS 0 NRROS 1 NRXN1 0 NSD1 0 NSD2 1 NSDHL 1 NSUN2 0 NT5C2 1 NTNG2 1 NTRK1 0 NTRK2 1 NUBPL 0 NUDT2 1 NUP188 1 NUP214 2 NUS1 1 OCLN 0 OCRL 0 ODC1 1 OFD1 0 OGT 1 OPA3 0 OPHN1 0 OSGEP 1 OTC 0 OTUD5 2 OTUD6B 0 OTX2 0 OXR1 1 P4HTM 1 PACS1 1 PACS2 1 PAFAH1B1 1 PAH 0 PAK1 1 PAK3 1 PAM16 1 PARN 0 PARP6 1 PAX6 0 PAX8 0 PBX1 0 PC 0 PCCA 0 PCCB 0 PCDH12 1 PCDH19 0 PCDHGC4 1 PCGF2 1 PCNT 0 PCYT2 1 PDE10A 1 PDE4D 0 PDE6D 1 PDGFRB 0 PDHA1 0 PDHB 1 PDHX 0 PDP1 1 PDSS1 1 PDSS2 0 PEPD 0 PET100 1 PEX1 0 PEX10 0 PEX11B 0 PEX12 0 PEX13 0 PEX14 0 PEX16 0 PEX19 0 PEX2 0 PEX26 0 PEX3 0 PEX5 0 PEX6 0 PEX7 0 PGAP1 0 PGAP2 1 PGAP3 1 PGK1 1 PGM2L1 1 PGM3 1 PHACTR1 1 PHF21A 2 PHF6 0 PHF8 1 PHGDH 0 PHIP 1 PI4KA 1 PIBF1 2 PIDD1 1 PIGA 1 PIGB 2 PIGC 1 PIGG 1 PIGH 1 PIGK 1 PIGL 1 PIGN 1 PIGO 1 PIGP 2 PIGQ 1 PIGS 1 PIGT 1 PIGU 1 PIGV 1 PIGW 0 PIK3C2A 1 PIK3CA 0 PIK3R2 1 PISD 1 PITRM1 1 PLA2G6 0 PLAA 0 PLCB1 1 PLK4 1 PLP1 0 PLPBP 1 PMM2 0 PMPCA 1 PMPCB 1 PNKP 1 PNPLA6 0 PNPT1 1 POGZ 1 POLA1 1 POLG 0 POLR1C 1 POLR2A 1 POLR3A 0 POLR3B 0 POLRMT 1 POMGNT1 0 POMGNT2 0 POMK 1 POMT1 0 POMT2 0 PORCN 0 POU3F3 1 PPIL1 1 PPM1D 1 PPP1CB 1 PPP1R12A 1 PPP1R15B 0 PPP1R21 1 PPP2CA 1 PPP2R1A 1 PPP2R5D 1 PPP3CA 0 PPT1 0 PQBP1 1 PRICKLE2 1 PRKAR1A 1 PRKAR1B 1 PRMT7 0 PRODH 0 PRPS1 0 PRR12 1 PRSS12 0 PRUNE1 1 PSAP 1 PSMD12 0 PSPH 0 PTCH1 0 PTCHD1 0 PTDSS1 0 PTEN 0 PTF1A 0 PTPN11 0 PTPN23 1 PTPN4 1 PTRHD1 1 PTS 0 PUF60 1 PUM1 1 PURA 1 PUS1 0 PUS3 1 PUS7 1 PYCR1 0 PYCR2 0 QARS 1 QDPR 0 QRICH1 1 RAB11B 1 RAB18 0 RAB23 0 RAB39B 0 RAB3GAP1 1 RAB3GAP2 0 RAC1 1 RAC3 1 RAD21 1 RAF1 0 RAI1 1 RALA 1 RALGAPA1 1 RAP1B 2 RARB 1 RARS 1 RARS2 0 RBBP8 0 RBM10 1 RELN 0 RERE 1 RFT1 1 RFX3 1 RFX4 1 RFX7 1 RHEB 1 RHOBTB2 1 RIT1 0 RLIM 1 RMND1 0 RNASEH2A 0 RNASEH2B 0 RNASEH2C 0 RNASET2 0 RNF125 0 RNF13 1 RNF220 1 RNU4ATAC 1 RNU7-1 2 ROGDI 1 ROR2 0 RORA 1 RPGRIP1L 0 RPIA 1 RPL10 1 RPS6KA3 0 RRM2B 0 RSRC1 1 RTEL1 0 RTN4IP1 1 RTTN 1 SAMD9 0 SAMHD1 0 SARS2 1 SATB1 2 SATB2 1 SBF1 1 SC5D 0 SCAF4 1 SCAMP5 2 SCAPER 1 SCN1A 1 SCN1B 1 SCN2A 0 SCN3A 1 SCN8A 0 SCO2 0 SDCCAG8 1 SDHA 0 SDHAF1 1 SEPSECS 1 SERAC1 0 SET 0 SETBP1 0 SETD1A 1 SETD1B 1 SETD2 1 SETD5 1 SFXN4 1 SGPL1 0 SGSH 1 SHANK2 0 SHANK3 1 SHH 0 SHMT2 2 SHOC2 1 SIAH1 1 SIK1 0 SIL1 1 SIN3A 0 SIN3B 1 SIX3 0 SKI 0 SLC12A2 3 SLC12A5 0 SLC12A6 0 SLC13A5 1 SLC16A2 1 SLC17A5 0 SLC18A2 1 SLC19A3 0 SLC1A1 1 SLC1A2 1 SLC1A4 1 SLC25A1 0 SLC25A12 0 SLC25A15 0 SLC25A22 0 SLC2A1 0 SLC33A1 0 SLC35A1 0 SLC35A2 0 SLC35C1 0 SLC39A14 0 SLC39A8 1 SLC46A1 1 SLC4A4 0 SLC5A6 1 SLC6A1 1 SLC6A17 0 SLC6A19 0 SLC6A3 0 SLC6A8 0 SLC6A9 1 SLC9A6 1 SLX4 0 SMAD4 0 SMARCA2 1 SMARCA4 0 SMARCA5 1 SMARCB1 0 SMARCC2 1 SMARCD1 1 SMARCE1 0 SMC1A 0 SMC3 0 SMG8 2 SMG9 1 SMOC1 1 SMPD1 1 SMPD4 1 SMS 0 SNAP25 1 SNAP29 0 SNRPB 1 SNX14 0 SNX27 1 SON 1 SOS1 1 SOS2 1 SOX10 0 SOX11 0 SOX2 1 SOX4 1 SOX5 1 SOX6 2 SOX9 0 SPART 1 SPATA5 1 SPECC1L 0 SPEN 2 SPG11 1 SPOP 1 SPR 0 SPRED1 1 SPTAN1 1 SPTBN1 1 SPTBN2 0 SPTBN4 2 SRCAP 2 SRD5A3 0 SSR4 0 ST3GAL3 0 ST3GAL5 2 STAG1 0 STAG2 1 STAMBP 1 STIL 1 STRA6 0 STRADA 1 STT3A 2 STX1B 0 STXBP1 0 SUCLA2 1 SUCLG1 0 SUFU 1 SUMF1 1 SUOX 0 SUPT16H 1 SURF1 0 SUZ12 2 SVBP 2 SYN1 0 SYNCRIP 2 SYNGAP1 1 SYNJ1 0 SYP 0 SYT1 2 SZT2 0 TAF1 1 TAF2 2 TAF6 1 TANC2 2 TANGO2 0 TAOK1 1 TASP1 1 TAT 0 TAZ 0 TBC1D20 1 TBC1D23 0 TBC1D24 0 TBCD 1 TBCE 0 TBCK 0 TBL1XR1 0 TBR1 1 TBX1 1 TCF20 1 TCF4 0 TCF7L2 2 TCN2 1 TCTN2 0 TCTN3 1 TDP2 1 TECPR2 1 TELO2 1 TENM3 1 TERT 2 TET3 1 TFE3 2 TGIF1 1 TH 0 THOC2 1 THOC6 0 THRA 0 TIMM50 1 TINF2 1 TLK2 1 TMCO1 0 TMEM106B 1 TMEM165 1 TMEM216 0 TMEM222 2 TMEM237 1 TMEM240 0 TMEM5 0 TMEM67 1 TMEM70 0 TMEM94 1 TMTC3 1 TMX2 1 TNPO2 1 TNR 1 TNRC6B 2 TOE1 1 TOGARAM1 1 TP73 1 TPP1 1 TPP2 1 TRAF7 1 TRAIP 1 TRAK1 1 TRAPPC11 1 TRAPPC12 1 TRAPPC4 1 TRAPPC6B 1 TRAPPC9 2 TREX1 0 TRIM8 1 TRIO 1 TRIP12 1 TRIT1 1 TRMT1 1 TRMT10A 1 TRNT1 1 TRPM3 1 TRRAP 1 TSC1 0 TSC2 0 TSEN15 1 TSEN2 0 TSEN54 0 TSFM 0 TSHB 0 TSPAN7 0 TSPOAP1 1 TTC19 0 TTC37 0 TTC5 2 TTC8 1 TTI2 1 TUBA1A 0 TUBB 1 TUBB2A 1 TUBB2B 0 TUBB3 0 TUBB4A 0 TUBG1 0 TUBGCP2 1 TUBGCP6 1 TUSC3 1 TWIST1 0 UBA5 0 UBE2A 1 UBE3A 0 UBE3B 1 UBE4A 1 UBR1 1 UBR7 1 UBTF 1 UFC1 1 UFM1 1 UFSP2 2 UGDH 1 UGP2 1 UMPS 1 UNC80 1 UPB1 2 UPF3B 2 USP18 1 USP7 2 USP9X 1 VAMP2 2 VARS 1 VARS2 1 VIPAS39 1 VLDLR 0 VPS11 1 VPS13B 0 VPS33B 1 VPS41 1 VPS4A 3 VPS53 0 VRK1 0 WAC 1 WARS2 1 WASF1 2 WASHC4 3 WDFY3 1 WDPCP 1 WDR11 2 WDR26 1 WDR37 1 WDR4 2 WDR45 0 WDR45B 1 WDR62 1 WDR73 0 WDR81 1 WNT1 1 WNT5A 2 WWOX 0 XPA 2 XRCC4 0 XYLT1 2 YARS 1 YIF1B 2 YWHAG 1 YY1 0 ZBTB18 0 ZBTB20 0 ZBTB24 1 ZC4H2 0 ZDHHC9 0 ZEB2 1 ZFHX4 1 ZFYVE26 0 ZIC1 1 ZIC2 0 ZMIZ1 2 ZMYM2 2 ZMYND11 1 ZNF142 1 ZNF148 1 ZNF292 2 ZNF335 1 ZNF462 2 ZNF526 1 ZNF699 1 ZNF711 1 ZSWIM6 1 AASS 1 ACADSB 1 ACAT1 1 ADAM22 1 AKAP6 1 ALDOA 1 ALX1 1 ALX3 1 ALX4 1 AP2S1 1 ARF3 2 ARHGAP31 1 ARHGAP35 1 ARNT2 1 ATP6V0A1 1 ATP9A 1 ATXN2L 1 B3GALT6 1 B9D1 1 BBIP1 1 C16orf62 1 C8orf37 1 CACNB4 1 CAPZA2 1 CCDC174 1 CCDC78 1 CD96 1 CDK16 1 CDK6 1 CDKN1C 1 CEP63 1 CEP89 1 CHRM1 1 CHST14 1 CLCN2 1 CNKSR1 1 COPB1 1 COQ2 1 COQ9 1 COX14 1 COX20 1 COX7B 1 CPE 1 CRBN 1 CTC1 1 CTNND1 1 CTNND2 1 DDOST 1 DHX32 1 DLAT 1 DPH2 1 DPP6 2 DSCAM 1 EEF1B2 1 EEF1D 1 EIF2A 1 EMG1 1 EMX2 1 EPHA7 1 ERGIC3 2 EXOC2 2 EXOSC2 1 FANCB 1 FANCD2 1 FANCG 1 FASTKD2 1 FEM1B 1 FGFR2 1 FIBP 1 FOXP4 1 FRMD4A 1 FRY 1 FTO 1 FUK 1 GBA 1 GEMIN4 1 GIGYF1 1 GMNN 1 GNAI2 1 GNAQ 1 GORAB 1 GPHN 1 GSX2 1 GTF2E2 2 HARS 2 HAX1 1 HEATR5B 1 HIST1H4J 1 HNRNPD 1 HSPA9 1 HTT 1 HYLS1 1 ICE1 1 IMPA1 1 INPP4A 1 IQSEC3 2 ITCH 1 ITFG2 2 ITGA7 1 JAKMIP1 1 KCNJ1 1 KLHL15 1 LAS1L 1 LINGO1 1 LIPT2 1 LMAN2L 1 LNPK 1 LRRC32 1 LYST 1 MAGT1 1 MMGT1 1 MRPL3 2 MSL2 1 NBN 1 NDUFA10 1 NDUFA11 1 NDUFA9 1 NDUFAF2 1 NDUFAF3 1 NDUFAF4 1 NDUFAF5 1 NDUFAF6 1 NDUFB3 1 NDUFB9 1 NDUFS2 1 NDUFS3 1 NDUFS6 1 NDUFV2 1 NECAP1 1 NHP2 1 NMNAT1 1 NR2F2 1 NSF 1 PAX1 1 PDCD6IP 1 PDE2A 1 PHC1 1 PIEZO2 1 PIGY 1 PJA1 1 PLCH1 1 PLEKHG2 1 PLOD3 1 PLXNA2 1 PPP2R5C 1 PRKACB 2 PRKD1 2 PRRT2 1 PSAT1 1 PSMB1 1 PSMC3 1 PSMC5 1 PTRH2 1 RAB11A 1 RAB14 1 RAP1GDS1 1 RIC1 1 RMRP 1 RNF113A 1 RNF2 1 RPS23 1 RSPRY1 1 RUSC2 1 SACS 1 SEC31A 1 SEMA3E 1 SEMA5A 1 SHROOM4 1 SLC2A2 1 SLC35A3 2 SLC45A1 1 SLC5A5 1 SLC9A7 1 SMARCD2 1 SNORD118 1 SNRPN 1 SOX3 2 SRRM2 1 STN1 1 TACO1 1 TAF13 1 TAF1C 1 TARS 1 TBC1D2B 2 TBC1D7 1 TGFB1 1 THRB 1 TKFC 1 TKT 2 TMEM231 1 TMLHE 1 TNIK 1 TOP2B 1 TRAPPC2L 1 TRIP13 1 TTI1 2 TUBGCP4 1 TUFM 1 U2AF2 1 UPF1 1 UQCC2 1 USP27X 1 VPS37A 1 VPS50 1 VPS51 1 WFS1 2 YAP1 1 ZBTB11 1 ZBTB16 1 ZC3H14 4 ZFHX3 2 ZNF407 2 ZNF668 1 ABCC6 2 ABCG5 1 ACOX2 1 ACTA1 1 ADA2 1 ADAMTSL2 1 ADCY5 1 ADGRB3 1 ADGRG6 2 ADRA2B 1 AFG3L2 1 AGGF1 1 AGK 1 AGL 1 AGO3 1 AGPS 1 AGT 1 AGTR2 1 AKR1C2 1 ALDOB 1 ALG2 1 ALS2 1 ANK3 1 ANKH 1 APTX 1 AR 1 ARHGEF6 1 ASMT 1 ATL1 1 ATP10A 1 ATP2A2 1 ATP2B3 1 ATP2C2 1 ATXN10 1 AVP 1 AVPR1A 1 AVPR2 1 B3GAT3 1 BDNF 1 BICD2 1 BIN1 1 BMPER 1 C19orf12 1 C3orf58 1 CA5A 1 CACNG2 1 CANT1 1 CCDC8 1 CDC6 1 CDK5R1 1 CDT1 1 CFH 1 CFHR1 1 CFHR3 1 CHRNA4 1 CISD2 1 CLCNKA 1 CLIC2 1 CLIP2 1 CLPP 1 CMAS 1 CNTN3 1 CNTN4 1 CNTN6 1 CNTNAP5 1 COA3 1 COL18A1 1 COL1A2 1 COLEC10 1 COQ5 1 CORO1A 1 COX4I2 1 COX6B1 1 CP 1 CPA6 1 CRKL 1 CRLF1 1 CRTAP 1 CTSF 1 CUBN 1 CYFIP1 1 CYP27A1 1 CYP2U1 1 DDR2 1 DISP1 1 DLGAP2 1 DLK1 2 DNAJA1 1 DNAJC3 1 DNAJC6 1 DOCK4 1 DOK7 1 DPM3 1 DPP10 1 DSCR3 1 DSE 1 DTYMK 1 DUOXA2 1 DYNC2H1 1 EDC3 1 EDNRB 1 EFNB1 1 EFNB2 1 EIF2AK1 1 EIF2B1 1 EIF2B2 1 EIF2B3 1 EIF2B4 1 EIF2B5 1 ELMOD1 1 EOGT 1 EOMES 1 EPB41L1 1 EPM2A 1 ERCC4 1 ERF 1 ERMARD 1 ETS1 1 EVC 1 EVC2 1 FA2H 1 FAAH2 1 FAM160B1 1 FBLN5 1 FBN1 1 FDXR 1 FGF3 1 FLNB 1 FLVCR1 1 FTL 1 FZD3 1 G6PC3 1 GABRG1 1 GAN 1 GATA1 1 GBA2 1 GBE1 1 GCK 1 GCSH 1 GHR 1 GJA1 1 GJB1 1 GLRA1 1 GLUD1 1 GNA14 1 GOSR2 1 GPSM2 1 GRPR 1 GSPT2 1 GTF2I 1 GTF2IRD1 1 GYS2 1 H19 1 HADH 1 HAL 1 HARS2 1 HOXD10 1 IFT140 1 IGBP1 1 IGF2 1 IMMP2L 1 INS 1 INSR 1 INTS8 1 IRX5 1 IYD 1 JAG1 1 JPH3 1 KANK1 1 KATNAL2 1 KCNC3 1 KCND3 1 KCTD13 1 KIF16B 1 KIF1B 1 KIF21A 1 KIF4A 1 KIRREL3 1 KLF8 1 KLLN 1 KYNU 1 LBR 1 LGI4 1 LHX3 1 LMNA 1 LRP5 1 LSM1 1 LSM11 2 MACROD2 1 MAP4K4 2 MARS2 2 MCM4 1 MEPCE 1 MET 1 METAP1 1 MFN2 1 MGME1 1 MGP 1 MID2 1 MLH1 1 MNX1 1 MPI 1 MPZ 1 MRAP 1 MRPS16 1 MSH6 1 MTM1 1 MTMR2 1 MTPAP 1 MYH3 1 MYMK 1 MYO7A 1 MYT1 1 NAGS 1 NDN 1 NEGR1 1 NGF 1 NHEJ1 1 NHLRC1 1 NIN 1 NLGN1 1 NLGN4X 1 NOP10 1 NOTCH3 1 NRXN2 1 NTNG1 1 NUP62 1 ORC1 1 ORC4 1 ORC6 1 OTUD7A 2 PANK2 1 PAX2 1 PAX3 1 PAX7 1 PCBD1 1 PCDH10 1 PCDH15 1 PCDH9 1 PCLO 1 PDE11A 1 PDGFB 1 PHKA2 1 PHKG2 1 PIGF 2 PIK3R1 1 PINK1 1 PIP5K1B 1 PNP 1 POC1A 1 POLD1 1 POLD2 1 PON3 1 POP1 1 POU1F1 1 PPM1K 1 PPOX 1 PRDM8 1 PREPL 1 PRF1 1 PRICKLE1 1 PRKDC 1 PRKN 1 PRKRA 1 PRRX1 1 PRX 1 PYGL 1 RAB27A 1 RAB40AL 1 RALGAPB 1 RANBP2 1 RAPSN 1 RASA1 2 RAX 1 RBFOX1 1 RBL2 1 RBM28 1 RBM8A 1 RBPJ 1 RECQL4 1 RET 1 RFX6 1 RIMS1 1 RIN2 1 RING1 1 RNF135 2 RPL11 1 RPS19 1 RPS28 1 RUBCN 1 SALL1 1 SAMD9L 1 SBDS 1 SCN11A 1 SCN9A 1 SCO1 1 SECISBP2 1 SELENOI 1 SELENON 1 SF3B4 1 SGCA 1 SH3TC2 1 SHANK1 1 SLC12A1 1 SLC19A2 1 SLC1A3 1 SLC20A2 1 SLC22A5 1 SLC25A13 1 SLC25A19 1 SLC25A20 1 SLC25A24 1 SLC25A4 2 SLC29A3 1 SLC2A10 1 SLC39A4 1 SLC44A1 2 SLC5A2 1 SLC6A4 1 SLC7A7 1 SLC9A9 1 SMCHD1 1 SMG6 1 SNIP1 1 SNRPA 1 SNRPE 2 SOBP 1 SOST 1 SP7 1 SPAST 1 SPEG 1 SPG7 2 SPINK5 1 SPRTN 1 SPTLC1 1 SRPX2 1 ST7 1 STAC3 1 STAT5B 1 STK3 1 STT3B 1 STX11 1 SYT14 1 TAF8 1 TDGF1 2 TECR 1 TFAP2A 1 TFAP2B 1 TFG 1 TG 1 TGFBR1 1 TGFBR2 1 THAP1 1 TIMM8A 1 TMEM260 1 TP63 1 TPH2 1 TPK1 1 TRAPPC6A 1 TREM2 1 TRHR 1 TRIM32 1 TRIM37 1 TSEN34 1 TSHR 1 TTC21B 1 TTR 1 TUBA8 1 TWNK 1 TXNL4A 1 UBE2U 1 UBR4 2 UCHL1 1 UGT1A1 1 UNC13A 1 UNC13D 1 UQCRB 1 UQCRC2 1 UQCRQ 1 UROC1 1 VAMP1 1 VANGL1 1 VPS45 1 WASHC5 1 WDR13 1 WDR19 1 WDR34 1 WIPI2 1 WRAP53 1 XIST 1 XPNPEP3 1 ZCCHC12 1 ZDHHC15 1 ZFP57 1 ZMYM3 1 ZNF41 1 ZNF423 1 ZNF507 1 ZNF674 1 ZNF804A 1 ZNF81 2 ZNHIT6 1 DIP2B 2 DMPK 2 Add a gene STRs in panel DM1 1 FRAXE 1 FRA12A 1 Add a STR Regions in panel Add a Region Intellectual disability syndromic and non-syndromic Gene: HMGB1 Green List (high evidence) You reviewed HMGB1 (high mobility group box 1) EnsemblGeneIds (GRCh38): ENSG00000189403 EnsemblGeneIds (GRCh37): ENSG00000189403 OMIM: 163905, Gene2Phenotype HMGB1 is in 3 panels Reviews (1) Details History Review feedback Review gene Rating: Rating Mode of Inheritance: Mode of Inheritance Mode of pathogenicity: Mode of pathogenicity Publications (PMID: 1234; 4321): Publications (PMID: 1234; 4321) Phenotypes (separate using a semi-colon -; ): Phenotypes (separate using a semi-colon -; ) Current diagnostic: Current diagnostic Comments: Comments 1 review Your review Chirag Patel (Genetic Health Queensland) Green List (high evidence) 13q12.3 microdeletion syndrome is a rare cause of syndromic ID. Previous studies identified four genes within the ~300 Kb minimal critical region including two candidate protein coding genes: KATNAL1 and HMGB1. Uguen et al. (2021) report 6 patients with LOF variants involving HMGB1 with features similar to 13q12.3 microdeletion syndrome (i.e. developmental delay, language delay, microcephaly, obesity and dysmorphic features). In silico analyses suggest that HMGB1 is likely to be intolerant to LOF, and previous in vitro data are in line with the role of HMGB1 in neurodevelopment. They suggest that haploinsufficiency of the HMGB1 gene may play a critical role in the pathogenesis of the 13q12.3 microdeletion syndrome. Sources: Literature Created: 17 Sep 2021, 4:56 a.m. Mode of inheritance MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes Developmental delay and microcephaly, no OMIM # to Developmental delay and microcephaly, no OMIM #
Microcephaly v1.50 HMGB1 Chirag Patel edited their review of gene: HMGB1: Changed phenotypes: Developmental delay and microcephaly, no OMIM #
Microcephaly v1.50 HMGB1 Chirag Patel Classified gene: HMGB1 as Green List (high evidence)
Microcephaly v1.50 HMGB1 Chirag Patel Gene: hmgb1 has been classified as Green List (High Evidence).
Microcephaly v1.49 HMGB1 Chirag Patel gene: HMGB1 was added
gene: HMGB1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: HMGB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HMGB1 were set to PMID: 34164801
Phenotypes for gene: HMGB1 were set to 0 ALDH5A1 1 ALDH7A1 0 ALG1 0 ALG11 1 ALG12 1 ALG13 1 ALG14 1 ALG3 1 ALG6 1 ALG8 1 ALG9 1 ALKBH8 1 ALMS1 0 AMER1 0 AMPD2 0 AMT 0 ANK2 2 ANKRD11 0 ANKRD17 2 AP1B1 1 AP1G1 1 AP1S1 0 AP1S2 0 AP2M1 1 AP3B1 0 AP3B2 1 AP4B1 1 AP4E1 1 AP4M1 1 AP4S1 1 APC2 1 APOPT1 1 ARCN1 1 ARF1 1 ARFGEF2 0 ARG1 0 ARHGEF9 1 ARID1A 1 ARID1B 1 ARID2 2 ARL13B 1 ARL6 1 ARMC9 1 ARSA 0 ARSB 1 ARSE 1 ARV1 0 ARX 0 ASAH1 0 ASH1L 1 ASL 1 ASNS 1 ASPA 0 ASPM 1 ASS1 0 ASTN1 1 ASXL1 0 ASXL2 0 ASXL3 1 ATAD1 1 ATAD3A 1 ATG7 1 ATIC 1 ATM 0 ATN1 1 ATP13A2 0 ATP1A1 1 ATP1A2 1 ATP1A3 2 ATP6AP1 1 ATP6AP2 0 ATP6V0A2 0 ATP6V1A 1 ATP6V1B2 0 ATP7A 0 ATP8A2 1 ATR 0 ATRX 0 AUH 0 AUTS2 1 B3GALNT2 1 B3GLCT 0 B4GALNT1 0 B4GALT1 1 B4GALT7 1 B9D2 1 BAZ2B 1 BBS1 0 BBS10 0 BBS12 0 BBS2 0 BBS4 1 BBS5 1 BBS7 1 BBS9 1 BCAP31 0 BCAS3 1 BCKDHA 0 BCKDHB 0 BCKDK 0 BCL11A 0 BCL11B 1 BCOR 1 BCORL1 1 BCS1L 0 BICRA 3 BLM 0 BMP4 0 BOLA3 0 BPTF 1 BRAF 0 BRAT1 1 BRD4 2 BRF1 1 BRIP1 1 BRPF1 1 BRSK2 1 BRWD3 0 BSCL2 0 BSND 1 BTD 0 BUB1B 0 C12orf4 0 C12orf57 0 C12orf65 0 C2CD3 1 C2orf69 1 C5orf42 1 CA2 1 CA8 1 CACNA1A 0 CACNA1B 1 CACNA1C 0 CACNA1D 1 CACNA1E 1 CACNA1G 2 CACNA1I 1 CACNA2D2 1 CAD 1 CAMK2A 0 CAMK2B 1 CAMK4 1 CAMTA1 2 CAPN15 1 CARS 1 CARS2 1 CASK 0 CBL 0 CBS 0 CBY1 1 CC2D1A 1 CC2D2A 0 CCBE1 1 CCDC22 0 CCDC47 1 CCDC88A 1 CCDC88C 2 CCND2 0 CDC42 0 CDC42BPB 1 CDH11 2 CDH15 0 CDH2 1 CDK10 0 CDK13 1 CDK19 1 CDK5RAP2 1 CDK8 1 CDKL5 0 CDON 0 CELF2 1 CENPF 0 CENPJ 0 CEP104 1 CEP120 1 CEP135 1 CEP152 1 CEP164 1 CEP290 0 CEP41 0 CEP55 1 CEP57 1 CEP83 1 CEP85L 1 CHAMP1 0 CHD1 1 CHD2 0 CHD3 1 CHD4 1 CHD5 1 CHD7 0 CHD8 0 CHKB 0 CHMP1A 1 CIC 0 CIT 0 CKAP2L 0 CLCN3 1 CLCN4 1 CLCN6 1 CLCNKB 1 CLN3 0 CLN5 1 CLN6 0 CLN8 0 CLP1 1 CLPB 1 CLTC 1 CNKSR2 0 CNNM2 0 CNOT1 3 CNOT2 1 CNOT3 2 CNPY3 1 CNTNAP1 1 CNTNAP2 0 COASY 1 COG1 0 COG4 1 COG5 1 COG6 1 COG7 0 COG8 1 COL4A1 0 COL4A2 0 COL4A3BP 0 COLEC11 0 COPB2 2 COQ4 0 COQ8A 0 COX10 1 COX15 0 CPS1 0 CRADD 1 CRB2 0 CREBBP 1 CSDE1 1 CSNK1G1 2 CSNK2A1 0 CSNK2B 0 CSPP1 1 CSTB 0 CTBP1 1 CTCF 1 CTDP1 0 CTNNA2 1 CTNNB1 0 CTSA 0 CTSD 0 CTU2 1 CUL3 2 CUL4B 0 CUX1 1 CUX2 1 CWC27 0 CWF19L1 1 CXorf56 1 CYB5R3 0 CYC1 0 CYFIP2 1 D2HGDH 0 DAG1 0 DARS 1 DARS2 0 DBT 0 DCAF17 0 DCHS1 0 DCPS 1 DCX 0 DDB1 2 DDC 0 DDHD2 0 DDX11 1 DDX23 2 DDX3X 0 DDX59 1 DDX6 1 DEAF1 1 DEGS1 1 DENND5A 1 DEPDC5 0 DHCR24 0 DHCR7 0 DHDDS 1 DHFR 1 DHPS 1 DHTKD1 0 DHX30 1 DHX37 2 DIAPH1 0 DIS3L2 0 DKC1 0 DLD 0 DLG3 1 DLG4 2 DLL1 1 DMD 0 DMXL2 1 DNAJC12 1 DNAJC19 0 DNM1 1 DNM1L 1 DNMT3A 1 DNMT3B 0 DOCK3 1 DOCK6 1 DOCK7 1 DOCK8 0 DOLK 1 DPAGT1 1 DPF2 0 DPH1 1 DPM1 0 DPM2 1 DPYD 1 DPYS 1 DPYSL5 1 DYM 1 DYNC1H1 0 DYNC1I2 1 DYRK1A 1 EARS2 1 EBF3 1 EBP 1 EDEM3 2 EED 1 EEF1A2 1 EEF2 1 EFTUD2 1 EHMT1 1 EIF2AK2 2 EIF2AK3 0 EIF2S3 1 EIF3F 1 EIF4A3 1 EIF5A 1 ELAC2 0 ELOVL4 0 ELP2 0 EMC1 1 EMC10 2 EML1 1 EP300 0 EPG5 1 ERCC1 1 ERCC2 0 ERCC3 0 ERCC5 1 ERCC6 0 ERCC6L2 0 ERCC8 0 ERLIN2 1 ESCO2 0 ETFA 1 ETFB 1 ETFDH 1 ETHE1 0 EXOC7 1 EXOSC3 0 EXOSC8 1 EXT2 1 EXTL3 1 EZH2 1 FAM111A 0 FAM126A 0 FAM20C 0 FAM50A 1 FAR1 1 FARS2 1 FARSA 1 FARSB 1 FAT4 0 FBRSL1 1 FBXL3 2 FBXL4 0 FBXO11 1 FBXO28 1 FBXO31 2 FBXW11 2 FBXW7 1 FDFT1 1 FGD1 1 FGF12 0 FGF13 1 FGF14 1 FGFR1 1 FGFR3 1 FH 0 FIG4 0 FITM2 1 FKRP 0 FKTN 0 FLNA 0 FLVCR2 0 FMN2 0 FMR1 0 FOLR1 1 FOXG1 0 FOXP1 2 FOXP2 1 FOXRED1 0 FRAS1 1 FRMPD4 1 FRRS1L 1 FTCD 1 FTSJ1 0 FUCA1 0 FUT8 1 GABBR2 1 GABRA1 1 GABRA2 1 GABRA5 1 GABRB2 0 GABRB3 1 GABRG2 1 GAD1 1 GALC 0 GALE 0 GALNT2 1 GALT 1 GAMT 0 GATA6 1 GATAD2B 1 GATM 1 GCDH 0 GCH1 0 GDI1 0 GEMIN5 1 GFAP 0 GFER 1 GFM1 0 GJC2 0 GK 0 GLB1 0 GLDC 0 GLI2 0 GLI3 0 GLIS3 1 GLS 1 GLUL 0 GLYCTK 0 GM2A 0 GMPPA 0 GMPPB 0 GNAI1 2 GNAO1 1 GNAS 1 GNB1 1 GNB2 3 GNB5 1 GNE 1 GNPAT 0 GNPTAB 0 GNPTG 1 GNS 0 GOLGA2 2 GOT2 1 GPAA1 1 GPC3 0 GPC4 1 GPT2 1 GRIA1 1 GRIA2 2 GRIA3 1 GRIA4 0 GRID2 0 GRIK2 1 GRIN1 1 GRIN2A 1 GRIN2B 1 GRIN2D 1 GRM1 0 GRM7 1 GSS 1 GTF2H5 0 GTF3C3 1 GTPBP2 1 GTPBP3 0 GUSB 1 H3F3A 1 H3F3B 1 HACE1 1 HADHA 0 HADHB 1 HCCS 0 HCFC1 0 HCN1 0 HDAC4 2 HDAC8 1 HECW2 2 HEPACAM 0 HERC1 0 HERC2 2 HESX1 0 HEXA 0 HEXB 0 HGSNAT 1 HIBCH 0 HID1 1 HIRA 1 HIST1H1E 1 HIST1H4C 2 HIVEP2 1 HK1 2 HLCS 0 HMGB1 1 HMGCL 0 HNMT 1 HNRNPH1 1 HNRNPH2 0 HNRNPK 0 HNRNPR 1 HNRNPU 1 HOXA1 0 HPD 0 HPDL 2 HPRT1 0 HRAS 1 HS2ST1 3 HSD17B10 0 HSD17B4 1 HSPD1 0 HSPG2 1 HTRA2 0 HUWE1 1 IARS 1 IBA57 1 IDH2 0 IDS 0 IDUA 0 IER3IP1 1 IFIH1 0 IFT172 0 IFT27 1 IFT74 1 IGF1 1 IGF1R 1 IKBKG 0 IL1RAPL1 0 IMPDH2 2 INPP5E 1 INPP5K 0 INTS1 1 IQSEC1 1 IQSEC2 1 IREB2 1 IRF2BPL 1 ISCA1 1 ISCA2 1 ISPD 0 ITPA 0 ITPR1 0 IVD 0 JAM3 1 JARID2 1 JMJD1C 2 KANSL1 1 KARS 1 KAT5 2 KAT6A 0 KAT6B 0 KAT8 1 KATNB1 1 KCNA2 1 KCNB1 1 KCNC1 0 KCNH1 1 KCNJ10 0 KCNJ11 0 KCNJ6 1 KCNK4 1 KCNK9 1 KCNMA1 1 KCNN2 1 KCNN3 1 KCNQ2 0 KCNQ3 1 KCNQ5 1 KCNT1 0 KCNT2 1 KCTD3 0 KCTD7 0 KDM1A 1 KDM3B 2 KDM4B 2 KDM5B 1 KDM5C 1 KDM6A 0 KDM6B 1 KIAA0586 0 KIAA1109 0 KIDINS220 1 KIF11 2 KIF14 1 KIF1A 2 KIF1BP 1 KIF21B 1 KIF2A 1 KIF5A 0 KIF5C 1 KIF7 0 KLF7 1 KLHL7 0 KMT2A 1 KMT2B 1 KMT2C 1 KMT2D 2 KMT2E 1 KMT5B 1 KNL1 1 KPTN 1 KRAS 0 L1CAM 0 L2HGDH 0 LAMA1 0 LAMA2 1 LAMB1 1 LAMB2 1 LAMC3 0 LAMP2 0 LARGE1 0 LARP7 1 LARS 2 LARS2 0 LIAS 1 LIG4 0 LINGO4 1 LINS1 0 LIPT1 1 LMBRD1 1 LMBRD2 2 LMNB1 2 LMNB2 2 LONP1 0 LRP2 0 LRPPRC 0 LSS 1 LTBP1 1 LYRM7 1 LZTFL1 1 LZTR1 1 MAB21L1 2 MAB21L2 1 MACF1 1 MADD 3 MAF 0 MAGEL2 1 MAN1B1 1 MAN2B1 1 MANBA 1 MAOA 1 MAP1B 1 MAP2K1 0 MAP2K2 0 MAPK1 2 MAPK8IP3 2 MAPKAPK5 1 MAPRE2 1 MASP1 1 MAST1 1 MAST3 1 MAT1A 0 MBD5 1 MBOAT7 0 MBTPS2 0 MCCC1 0 MCCC2 0 MCM3AP 1 MCOLN1 1 MCPH1 1 MDH2 0 MECP2 1 MED12 0 MED12L 1 MED13 1 MED13L 0 MED17 1 MED23 0 MED25 1 MED27 2 MEF2C 1 MEGF8 2 MEIS2 0 METTL23 2 METTL5 1 MFF 0 MFSD2A 1 MFSD8 1 MGAT2 1 MICU1 1 MID1 0 MIR17HG 2 MKKS 0 MKS1 0 MLC1 0 MLYCD 1 MMAA 0 MMAB 0 MMACHC 0 MMADHC 0 MN1 2 MOCS1 1 MOCS2 0 MOGS 1 MORC2 2 MPDU1 1 MPDZ 1 MPLKIP 1 MPP5 1 MPV17 1 MRPS22 0 MRPS34 1 MSL3 1 MSMO1 1 MTFMT 0 MTHFR 0 MTHFS 1 MTO1 1 MTOR 0 MTR 1 MTRR 1 MUT 0 MVK 0 MYCN 0 MYO5A 0 MYT1L 2 NAA10 0 NAA15 1 NACC1 0 NAGA 0 NAGLU 0 NALCN 0 NANS 0 NARS 2 NBEA 1 NCAPD2 2 NCAPG2 1 NCDN 2 NCKAP1 1 NDE1 1 NDP 0 NDST1 0 NDUFA1 0 NDUFA2 1 NDUFAF1 1 NDUFS1 1 NDUFS4 1 NDUFS7 0 NDUFS8 0 NDUFV1 0 NEDD4L 1 NEMF 2 NEU1 0 NEUROD2 1 NEXMIF 1 NF1 0 NFASC 1 NFIA 0 NFIB 1 NFIX 0 NFU1 1 NGLY1 0 NHS 0 NIPBL 1 NKAP 1 NKX2-1 0 NLGN3 0 NONO 0 NOVA2 1 NPC1 0 NPC2 0 NPHP1 0 NPHP3 1 NR2F1 1 NR4A2 2 NRAS 0 NRROS 1 NRXN1 0 NSD1 0 NSD2 1 NSDHL 1 NSUN2 0 NT5C2 1 NTNG2 1 NTRK1 0 NTRK2 1 NUBPL 0 NUDT2 1 NUP188 1 NUP214 2 NUS1 1 OCLN 0 OCRL 0 ODC1 1 OFD1 0 OGT 1 OPA3 0 OPHN1 0 OSGEP 1 OTC 0 OTUD5 2 OTUD6B 0 OTX2 0 OXR1 1 P4HTM 1 PACS1 1 PACS2 1 PAFAH1B1 1 PAH 0 PAK1 1 PAK3 1 PAM16 1 PARN 0 PARP6 1 PAX6 0 PAX8 0 PBX1 0 PC 0 PCCA 0 PCCB 0 PCDH12 1 PCDH19 0 PCDHGC4 1 PCGF2 1 PCNT 0 PCYT2 1 PDE10A 1 PDE4D 0 PDE6D 1 PDGFRB 0 PDHA1 0 PDHB 1 PDHX 0 PDP1 1 PDSS1 1 PDSS2 0 PEPD 0 PET100 1 PEX1 0 PEX10 0 PEX11B 0 PEX12 0 PEX13 0 PEX14 0 PEX16 0 PEX19 0 PEX2 0 PEX26 0 PEX3 0 PEX5 0 PEX6 0 PEX7 0 PGAP1 0 PGAP2 1 PGAP3 1 PGK1 1 PGM2L1 1 PGM3 1 PHACTR1 1 PHF21A 2 PHF6 0 PHF8 1 PHGDH 0 PHIP 1 PI4KA 1 PIBF1 2 PIDD1 1 PIGA 1 PIGB 2 PIGC 1 PIGG 1 PIGH 1 PIGK 1 PIGL 1 PIGN 1 PIGO 1 PIGP 2 PIGQ 1 PIGS 1 PIGT 1 PIGU 1 PIGV 1 PIGW 0 PIK3C2A 1 PIK3CA 0 PIK3R2 1 PISD 1 PITRM1 1 PLA2G6 0 PLAA 0 PLCB1 1 PLK4 1 PLP1 0 PLPBP 1 PMM2 0 PMPCA 1 PMPCB 1 PNKP 1 PNPLA6 0 PNPT1 1 POGZ 1 POLA1 1 POLG 0 POLR1C 1 POLR2A 1 POLR3A 0 POLR3B 0 POLRMT 1 POMGNT1 0 POMGNT2 0 POMK 1 POMT1 0 POMT2 0 PORCN 0 POU3F3 1 PPIL1 1 PPM1D 1 PPP1CB 1 PPP1R12A 1 PPP1R15B 0 PPP1R21 1 PPP2CA 1 PPP2R1A 1 PPP2R5D 1 PPP3CA 0 PPT1 0 PQBP1 1 PRICKLE2 1 PRKAR1A 1 PRKAR1B 1 PRMT7 0 PRODH 0 PRPS1 0 PRR12 1 PRSS12 0 PRUNE1 1 PSAP 1 PSMD12 0 PSPH 0 PTCH1 0 PTCHD1 0 PTDSS1 0 PTEN 0 PTF1A 0 PTPN11 0 PTPN23 1 PTPN4 1 PTRHD1 1 PTS 0 PUF60 1 PUM1 1 PURA 1 PUS1 0 PUS3 1 PUS7 1 PYCR1 0 PYCR2 0 QARS 1 QDPR 0 QRICH1 1 RAB11B 1 RAB18 0 RAB23 0 RAB39B 0 RAB3GAP1 1 RAB3GAP2 0 RAC1 1 RAC3 1 RAD21 1 RAF1 0 RAI1 1 RALA 1 RALGAPA1 1 RAP1B 2 RARB 1 RARS 1 RARS2 0 RBBP8 0 RBM10 1 RELN 0 RERE 1 RFT1 1 RFX3 1 RFX4 1 RFX7 1 RHEB 1 RHOBTB2 1 RIT1 0 RLIM 1 RMND1 0 RNASEH2A 0 RNASEH2B 0 RNASEH2C 0 RNASET2 0 RNF125 0 RNF13 1 RNF220 1 RNU4ATAC 1 RNU7-1 2 ROGDI 1 ROR2 0 RORA 1 RPGRIP1L 0 RPIA 1 RPL10 1 RPS6KA3 0 RRM2B 0 RSRC1 1 RTEL1 0 RTN4IP1 1 RTTN 1 SAMD9 0 SAMHD1 0 SARS2 1 SATB1 2 SATB2 1 SBF1 1 SC5D 0 SCAF4 1 SCAMP5 2 SCAPER 1 SCN1A 1 SCN1B 1 SCN2A 0 SCN3A 1 SCN8A 0 SCO2 0 SDCCAG8 1 SDHA 0 SDHAF1 1 SEPSECS 1 SERAC1 0 SET 0 SETBP1 0 SETD1A 1 SETD1B 1 SETD2 1 SETD5 1 SFXN4 1 SGPL1 0 SGSH 1 SHANK2 0 SHANK3 1 SHH 0 SHMT2 2 SHOC2 1 SIAH1 1 SIK1 0 SIL1 1 SIN3A 0 SIN3B 1 SIX3 0 SKI 0 SLC12A2 3 SLC12A5 0 SLC12A6 0 SLC13A5 1 SLC16A2 1 SLC17A5 0 SLC18A2 1 SLC19A3 0 SLC1A1 1 SLC1A2 1 SLC1A4 1 SLC25A1 0 SLC25A12 0 SLC25A15 0 SLC25A22 0 SLC2A1 0 SLC33A1 0 SLC35A1 0 SLC35A2 0 SLC35C1 0 SLC39A14 0 SLC39A8 1 SLC46A1 1 SLC4A4 0 SLC5A6 1 SLC6A1 1 SLC6A17 0 SLC6A19 0 SLC6A3 0 SLC6A8 0 SLC6A9 1 SLC9A6 1 SLX4 0 SMAD4 0 SMARCA2 1 SMARCA4 0 SMARCA5 1 SMARCB1 0 SMARCC2 1 SMARCD1 1 SMARCE1 0 SMC1A 0 SMC3 0 SMG8 2 SMG9 1 SMOC1 1 SMPD1 1 SMPD4 1 SMS 0 SNAP25 1 SNAP29 0 SNRPB 1 SNX14 0 SNX27 1 SON 1 SOS1 1 SOS2 1 SOX10 0 SOX11 0 SOX2 1 SOX4 1 SOX5 1 SOX6 2 SOX9 0 SPART 1 SPATA5 1 SPECC1L 0 SPEN 2 SPG11 1 SPOP 1 SPR 0 SPRED1 1 SPTAN1 1 SPTBN1 1 SPTBN2 0 SPTBN4 2 SRCAP 2 SRD5A3 0 SSR4 0 ST3GAL3 0 ST3GAL5 2 STAG1 0 STAG2 1 STAMBP 1 STIL 1 STRA6 0 STRADA 1 STT3A 2 STX1B 0 STXBP1 0 SUCLA2 1 SUCLG1 0 SUFU 1 SUMF1 1 SUOX 0 SUPT16H 1 SURF1 0 SUZ12 2 SVBP 2 SYN1 0 SYNCRIP 2 SYNGAP1 1 SYNJ1 0 SYP 0 SYT1 2 SZT2 0 TAF1 1 TAF2 2 TAF6 1 TANC2 2 TANGO2 0 TAOK1 1 TASP1 1 TAT 0 TAZ 0 TBC1D20 1 TBC1D23 0 TBC1D24 0 TBCD 1 TBCE 0 TBCK 0 TBL1XR1 0 TBR1 1 TBX1 1 TCF20 1 TCF4 0 TCF7L2 2 TCN2 1 TCTN2 0 TCTN3 1 TDP2 1 TECPR2 1 TELO2 1 TENM3 1 TERT 2 TET3 1 TFE3 2 TGIF1 1 TH 0 THOC2 1 THOC6 0 THRA 0 TIMM50 1 TINF2 1 TLK2 1 TMCO1 0 TMEM106B 1 TMEM165 1 TMEM216 0 TMEM222 2 TMEM237 1 TMEM240 0 TMEM5 0 TMEM67 1 TMEM70 0 TMEM94 1 TMTC3 1 TMX2 1 TNPO2 1 TNR 1 TNRC6B 2 TOE1 1 TOGARAM1 1 TP73 1 TPP1 1 TPP2 1 TRAF7 1 TRAIP 1 TRAK1 1 TRAPPC11 1 TRAPPC12 1 TRAPPC4 1 TRAPPC6B 1 TRAPPC9 2 TREX1 0 TRIM8 1 TRIO 1 TRIP12 1 TRIT1 1 TRMT1 1 TRMT10A 1 TRNT1 1 TRPM3 1 TRRAP 1 TSC1 0 TSC2 0 TSEN15 1 TSEN2 0 TSEN54 0 TSFM 0 TSHB 0 TSPAN7 0 TSPOAP1 1 TTC19 0 TTC37 0 TTC5 2 TTC8 1 TTI2 1 TUBA1A 0 TUBB 1 TUBB2A 1 TUBB2B 0 TUBB3 0 TUBB4A 0 TUBG1 0 TUBGCP2 1 TUBGCP6 1 TUSC3 1 TWIST1 0 UBA5 0 UBE2A 1 UBE3A 0 UBE3B 1 UBE4A 1 UBR1 1 UBR7 1 UBTF 1 UFC1 1 UFM1 1 UFSP2 2 UGDH 1 UGP2 1 UMPS 1 UNC80 1 UPB1 2 UPF3B 2 USP18 1 USP7 2 USP9X 1 VAMP2 2 VARS 1 VARS2 1 VIPAS39 1 VLDLR 0 VPS11 1 VPS13B 0 VPS33B 1 VPS41 1 VPS4A 3 VPS53 0 VRK1 0 WAC 1 WARS2 1 WASF1 2 WASHC4 3 WDFY3 1 WDPCP 1 WDR11 2 WDR26 1 WDR37 1 WDR4 2 WDR45 0 WDR45B 1 WDR62 1 WDR73 0 WDR81 1 WNT1 1 WNT5A 2 WWOX 0 XPA 2 XRCC4 0 XYLT1 2 YARS 1 YIF1B 2 YWHAG 1 YY1 0 ZBTB18 0 ZBTB20 0 ZBTB24 1 ZC4H2 0 ZDHHC9 0 ZEB2 1 ZFHX4 1 ZFYVE26 0 ZIC1 1 ZIC2 0 ZMIZ1 2 ZMYM2 2 ZMYND11 1 ZNF142 1 ZNF148 1 ZNF292 2 ZNF335 1 ZNF462 2 ZNF526 1 ZNF699 1 ZNF711 1 ZSWIM6 1 AASS 1 ACADSB 1 ACAT1 1 ADAM22 1 AKAP6 1 ALDOA 1 ALX1 1 ALX3 1 ALX4 1 AP2S1 1 ARF3 2 ARHGAP31 1 ARHGAP35 1 ARNT2 1 ATP6V0A1 1 ATP9A 1 ATXN2L 1 B3GALT6 1 B9D1 1 BBIP1 1 C16orf62 1 C8orf37 1 CACNB4 1 CAPZA2 1 CCDC174 1 CCDC78 1 CD96 1 CDK16 1 CDK6 1 CDKN1C 1 CEP63 1 CEP89 1 CHRM1 1 CHST14 1 CLCN2 1 CNKSR1 1 COPB1 1 COQ2 1 COQ9 1 COX14 1 COX20 1 COX7B 1 CPE 1 CRBN 1 CTC1 1 CTNND1 1 CTNND2 1 DDOST 1 DHX32 1 DLAT 1 DPH2 1 DPP6 2 DSCAM 1 EEF1B2 1 EEF1D 1 EIF2A 1 EMG1 1 EMX2 1 EPHA7 1 ERGIC3 2 EXOC2 2 EXOSC2 1 FANCB 1 FANCD2 1 FANCG 1 FASTKD2 1 FEM1B 1 FGFR2 1 FIBP 1 FOXP4 1 FRMD4A 1 FRY 1 FTO 1 FUK 1 GBA 1 GEMIN4 1 GIGYF1 1 GMNN 1 GNAI2 1 GNAQ 1 GORAB 1 GPHN 1 GSX2 1 GTF2E2 2 HARS 2 HAX1 1 HEATR5B 1 HIST1H4J 1 HNRNPD 1 HSPA9 1 HTT 1 HYLS1 1 ICE1 1 IMPA1 1 INPP4A 1 IQSEC3 2 ITCH 1 ITFG2 2 ITGA7 1 JAKMIP1 1 KCNJ1 1 KLHL15 1 LAS1L 1 LINGO1 1 LIPT2 1 LMAN2L 1 LNPK 1 LRRC32 1 LYST 1 MAGT1 1 MMGT1 1 MRPL3 2 MSL2 1 NBN 1 NDUFA10 1 NDUFA11 1 NDUFA9 1 NDUFAF2 1 NDUFAF3 1 NDUFAF4 1 NDUFAF5 1 NDUFAF6 1 NDUFB3 1 NDUFB9 1 NDUFS2 1 NDUFS3 1 NDUFS6 1 NDUFV2 1 NECAP1 1 NHP2 1 NMNAT1 1 NR2F2 1 NSF 1 PAX1 1 PDCD6IP 1 PDE2A 1 PHC1 1 PIEZO2 1 PIGY 1 PJA1 1 PLCH1 1 PLEKHG2 1 PLOD3 1 PLXNA2 1 PPP2R5C 1 PRKACB 2 PRKD1 2 PRRT2 1 PSAT1 1 PSMB1 1 PSMC3 1 PSMC5 1 PTRH2 1 RAB11A 1 RAB14 1 RAP1GDS1 1 RIC1 1 RMRP 1 RNF113A 1 RNF2 1 RPS23 1 RSPRY1 1 RUSC2 1 SACS 1 SEC31A 1 SEMA3E 1 SEMA5A 1 SHROOM4 1 SLC2A2 1 SLC35A3 2 SLC45A1 1 SLC5A5 1 SLC9A7 1 SMARCD2 1 SNORD118 1 SNRPN 1 SOX3 2 SRRM2 1 STN1 1 TACO1 1 TAF13 1 TAF1C 1 TARS 1 TBC1D2B 2 TBC1D7 1 TGFB1 1 THRB 1 TKFC 1 TKT 2 TMEM231 1 TMLHE 1 TNIK 1 TOP2B 1 TRAPPC2L 1 TRIP13 1 TTI1 2 TUBGCP4 1 TUFM 1 U2AF2 1 UPF1 1 UQCC2 1 USP27X 1 VPS37A 1 VPS50 1 VPS51 1 WFS1 2 YAP1 1 ZBTB11 1 ZBTB16 1 ZC3H14 4 ZFHX3 2 ZNF407 2 ZNF668 1 ABCC6 2 ABCG5 1 ACOX2 1 ACTA1 1 ADA2 1 ADAMTSL2 1 ADCY5 1 ADGRB3 1 ADGRG6 2 ADRA2B 1 AFG3L2 1 AGGF1 1 AGK 1 AGL 1 AGO3 1 AGPS 1 AGT 1 AGTR2 1 AKR1C2 1 ALDOB 1 ALG2 1 ALS2 1 ANK3 1 ANKH 1 APTX 1 AR 1 ARHGEF6 1 ASMT 1 ATL1 1 ATP10A 1 ATP2A2 1 ATP2B3 1 ATP2C2 1 ATXN10 1 AVP 1 AVPR1A 1 AVPR2 1 B3GAT3 1 BDNF 1 BICD2 1 BIN1 1 BMPER 1 C19orf12 1 C3orf58 1 CA5A 1 CACNG2 1 CANT1 1 CCDC8 1 CDC6 1 CDK5R1 1 CDT1 1 CFH 1 CFHR1 1 CFHR3 1 CHRNA4 1 CISD2 1 CLCNKA 1 CLIC2 1 CLIP2 1 CLPP 1 CMAS 1 CNTN3 1 CNTN4 1 CNTN6 1 CNTNAP5 1 COA3 1 COL18A1 1 COL1A2 1 COLEC10 1 COQ5 1 CORO1A 1 COX4I2 1 COX6B1 1 CP 1 CPA6 1 CRKL 1 CRLF1 1 CRTAP 1 CTSF 1 CUBN 1 CYFIP1 1 CYP27A1 1 CYP2U1 1 DDR2 1 DISP1 1 DLGAP2 1 DLK1 2 DNAJA1 1 DNAJC3 1 DNAJC6 1 DOCK4 1 DOK7 1 DPM3 1 DPP10 1 DSCR3 1 DSE 1 DTYMK 1 DUOXA2 1 DYNC2H1 1 EDC3 1 EDNRB 1 EFNB1 1 EFNB2 1 EIF2AK1 1 EIF2B1 1 EIF2B2 1 EIF2B3 1 EIF2B4 1 EIF2B5 1 ELMOD1 1 EOGT 1 EOMES 1 EPB41L1 1 EPM2A 1 ERCC4 1 ERF 1 ERMARD 1 ETS1 1 EVC 1 EVC2 1 FA2H 1 FAAH2 1 FAM160B1 1 FBLN5 1 FBN1 1 FDXR 1 FGF3 1 FLNB 1 FLVCR1 1 FTL 1 FZD3 1 G6PC3 1 GABRG1 1 GAN 1 GATA1 1 GBA2 1 GBE1 1 GCK 1 GCSH 1 GHR 1 GJA1 1 GJB1 1 GLRA1 1 GLUD1 1 GNA14 1 GOSR2 1 GPSM2 1 GRPR 1 GSPT2 1 GTF2I 1 GTF2IRD1 1 GYS2 1 H19 1 HADH 1 HAL 1 HARS2 1 HOXD10 1 IFT140 1 IGBP1 1 IGF2 1 IMMP2L 1 INS 1 INSR 1 INTS8 1 IRX5 1 IYD 1 JAG1 1 JPH3 1 KANK1 1 KATNAL2 1 KCNC3 1 KCND3 1 KCTD13 1 KIF16B 1 KIF1B 1 KIF21A 1 KIF4A 1 KIRREL3 1 KLF8 1 KLLN 1 KYNU 1 LBR 1 LGI4 1 LHX3 1 LMNA 1 LRP5 1 LSM1 1 LSM11 2 MACROD2 1 MAP4K4 2 MARS2 2 MCM4 1 MEPCE 1 MET 1 METAP1 1 MFN2 1 MGME1 1 MGP 1 MID2 1 MLH1 1 MNX1 1 MPI 1 MPZ 1 MRAP 1 MRPS16 1 MSH6 1 MTM1 1 MTMR2 1 MTPAP 1 MYH3 1 MYMK 1 MYO7A 1 MYT1 1 NAGS 1 NDN 1 NEGR1 1 NGF 1 NHEJ1 1 NHLRC1 1 NIN 1 NLGN1 1 NLGN4X 1 NOP10 1 NOTCH3 1 NRXN2 1 NTNG1 1 NUP62 1 ORC1 1 ORC4 1 ORC6 1 OTUD7A 2 PANK2 1 PAX2 1 PAX3 1 PAX7 1 PCBD1 1 PCDH10 1 PCDH15 1 PCDH9 1 PCLO 1 PDE11A 1 PDGFB 1 PHKA2 1 PHKG2 1 PIGF 2 PIK3R1 1 PINK1 1 PIP5K1B 1 PNP 1 POC1A 1 POLD1 1 POLD2 1 PON3 1 POP1 1 POU1F1 1 PPM1K 1 PPOX 1 PRDM8 1 PREPL 1 PRF1 1 PRICKLE1 1 PRKDC 1 PRKN 1 PRKRA 1 PRRX1 1 PRX 1 PYGL 1 RAB27A 1 RAB40AL 1 RALGAPB 1 RANBP2 1 RAPSN 1 RASA1 2 RAX 1 RBFOX1 1 RBL2 1 RBM28 1 RBM8A 1 RBPJ 1 RECQL4 1 RET 1 RFX6 1 RIMS1 1 RIN2 1 RING1 1 RNF135 2 RPL11 1 RPS19 1 RPS28 1 RUBCN 1 SALL1 1 SAMD9L 1 SBDS 1 SCN11A 1 SCN9A 1 SCO1 1 SECISBP2 1 SELENOI 1 SELENON 1 SF3B4 1 SGCA 1 SH3TC2 1 SHANK1 1 SLC12A1 1 SLC19A2 1 SLC1A3 1 SLC20A2 1 SLC22A5 1 SLC25A13 1 SLC25A19 1 SLC25A20 1 SLC25A24 1 SLC25A4 2 SLC29A3 1 SLC2A10 1 SLC39A4 1 SLC44A1 2 SLC5A2 1 SLC6A4 1 SLC7A7 1 SLC9A9 1 SMCHD1 1 SMG6 1 SNIP1 1 SNRPA 1 SNRPE 2 SOBP 1 SOST 1 SP7 1 SPAST 1 SPEG 1 SPG7 2 SPINK5 1 SPRTN 1 SPTLC1 1 SRPX2 1 ST7 1 STAC3 1 STAT5B 1 STK3 1 STT3B 1 STX11 1 SYT14 1 TAF8 1 TDGF1 2 TECR 1 TFAP2A 1 TFAP2B 1 TFG 1 TG 1 TGFBR1 1 TGFBR2 1 THAP1 1 TIMM8A 1 TMEM260 1 TP63 1 TPH2 1 TPK1 1 TRAPPC6A 1 TREM2 1 TRHR 1 TRIM32 1 TRIM37 1 TSEN34 1 TSHR 1 TTC21B 1 TTR 1 TUBA8 1 TWNK 1 TXNL4A 1 UBE2U 1 UBR4 2 UCHL1 1 UGT1A1 1 UNC13A 1 UNC13D 1 UQCRB 1 UQCRC2 1 UQCRQ 1 UROC1 1 VAMP1 1 VANGL1 1 VPS45 1 WASHC5 1 WDR13 1 WDR19 1 WDR34 1 WIPI2 1 WRAP53 1 XIST 1 XPNPEP3 1 ZCCHC12 1 ZDHHC15 1 ZFP57 1 ZMYM3 1 ZNF41 1 ZNF423 1 ZNF507 1 ZNF674 1 ZNF804A 1 ZNF81 2 ZNHIT6 1 DIP2B 2 DMPK 2 Add a gene STRs in panel DM1 1 FRAXE 1 FRA12A 1 Add a STR Regions in panel Add a Region Intellectual disability syndromic and non-syndromic Gene: HMGB1 Green List (high evidence) You reviewed HMGB1 (high mobility group box 1) EnsemblGeneIds (GRCh38): ENSG00000189403 EnsemblGeneIds (GRCh37): ENSG00000189403 OMIM: 163905, Gene2Phenotype HMGB1 is in 3 panels Reviews (1) Details History Review feedback Review gene Rating: Rating Mode of Inheritance: Mode of Inheritance Mode of pathogenicity: Mode of pathogenicity Publications (PMID: 1234; 4321): Publications (PMID: 1234; 4321) Phenotypes (separate using a semi-colon -; ): Phenotypes (separate using a semi-colon -; ) Current diagnostic: Current diagnostic Comments: Comments 1 review Your review Chirag Patel (Genetic Health Queensland) Green List (high evidence) 13q12.3 microdeletion syndrome is a rare cause of syndromic ID. Previous studies identified four genes within the ~300 Kb minimal critical region including two candidate protein coding genes: KATNAL1 and HMGB1. Uguen et al. (2021) report 6 patients with LOF variants involving HMGB1 with features similar to 13q12.3 microdeletion syndrome (i.e. developmental delay, language delay, microcephaly, obesity and dysmorphic features). In silico analyses suggest that HMGB1 is likely to be intolerant to LOF, and previous in vitro data are in line with the role of HMGB1 in neurodevelopment. They suggest that haploinsufficiency of the HMGB1 gene may play a critical role in the pathogenesis of the 13q12.3 microdeletion syndrome. Sources: Literature Created: 17 Sep 2021, 4:56 a.m. Mode of inheritance MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes Developmental delay and microcephaly, no OMIM #
Review for gene: HMGB1 was set to GREEN
Added comment: 13q12.3 microdeletion syndrome is a rare cause of syndromic ID. Previous studies identified four genes within the ~300 Kb minimal critical region including two candidate protein coding genes: KATNAL1 and HMGB1. Uguen et al. (2021) report 6 patients with LOF variants involving HMGB1 with features similar to 13q12.3 microdeletion syndrome (i.e. developmental delay, language delay, microcephaly, obesity and dysmorphic features). In silico analyses suggest that HMGB1 is likely to be intolerant to LOF, and previous in vitro data are in line with the role of HMGB1 in neurodevelopment. They suggest that haploinsufficiency of the HMGB1 gene may play a critical role in the pathogenesis of the 13q12.3 microdeletion syndrome.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4120 HMGB1 Chirag Patel Classified gene: HMGB1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4120 HMGB1 Chirag Patel Gene: hmgb1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4119 HMGB1 Chirag Patel gene: HMGB1 was added
gene: HMGB1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: HMGB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HMGB1 were set to PMID: 34164801
Phenotypes for gene: HMGB1 were set to Developmental delay and microcephaly, no OMIM #
Review for gene: HMGB1 was set to GREEN
Added comment: 13q12.3 microdeletion syndrome is a rare cause of syndromic ID. Previous studies identified four genes within the ~300 Kb minimal critical region including two candidate protein coding genes: KATNAL1 and HMGB1. Uguen et al. (2021) report 6 patients with LOF variants involving HMGB1 with features similar to 13q12.3 microdeletion syndrome (i.e. developmental delay, language delay, microcephaly, obesity and dysmorphic features). In silico analyses suggest that HMGB1 is likely to be intolerant to LOF, and previous in vitro data are in line with the role of HMGB1 in neurodevelopment. They suggest that haploinsufficiency of the HMGB1 gene may play a critical role in the pathogenesis of the 13q12.3 microdeletion syndrome.
Sources: Literature
Arthrogryposis v0.296 ERGIC1 Chirag Patel Classified gene: ERGIC1 as Amber List (moderate evidence)
Arthrogryposis v0.296 ERGIC1 Chirag Patel Gene: ergic1 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.295 ERGIC1 Chirag Patel gene: ERGIC1 was added
gene: ERGIC1 was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: ERGIC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERGIC1 were set to PMID: 28317099, 34037256
Phenotypes for gene: ERGIC1 were set to Arthrogryposis multiplex congenita 2, neurogenic type; OMIM # 208100
Review for gene: ERGIC1 was set to AMBER
Added comment: Reinstein et al. (2018) used WES in a large consanguineous Israeli Arab kindred consisting of 16 patients affected with the neurogenic type of arthrogryposis multiplex congenita. They identified a homozygous missense (V98E) mutation in ERGIC1 gene, which segregated with the disorder in the kindred, and was not found in the ExAC database or in 212 ethnically matched controls. Functional studies of the variant and studies of patient cells were not performed. ERGIC1 encodes a cycling membrane protein which has a possible role in transport between endoplasmic reticulum and Golgi.

Marconi et al (2021) used genome sequencing in a consanguineous family with 2 affected siblings presenting congenital arthrogryposis and some facial dysmorphism. They identified a homozygous 22.6 Kb deletion encompassing the promoter and first exon of ERGIC1. mRNA quantification showed the complete absence of ERGIC1 expression in the two affected siblings and a decrease in heterozygous parents.
Sources: Literature
Imprinting disorders v0.3 UBE3A Anna Le Fevre reviewed gene: UBE3A: Rating: GREEN; Mode of pathogenicity: None; Publications: 8988171, 16470747; Phenotypes: Angelman syndrome OMIM#105830; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Microcephaly v1.48 TAF2 Chirag Patel Classified gene: TAF2 as Green List (high evidence)
Microcephaly v1.48 TAF2 Chirag Patel Gene: taf2 has been classified as Green List (High Evidence).
Microcephaly v1.47 TAF2 Chirag Patel Classified gene: TAF2 as Green List (high evidence)
Microcephaly v1.47 TAF2 Chirag Patel Gene: taf2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4118 TAF2 Chirag Patel Classified gene: TAF2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4118 TAF2 Chirag Patel Gene: taf2 has been classified as Green List (High Evidence).
Imprinting disorders v0.3 ZFP57 Anna Le Fevre reviewed gene: ZFP57: Rating: GREEN; Mode of pathogenicity: None; Publications: 18622393, 27075368, 23150280, 30315371, 31399135, 33053156; Phenotypes: Transient Neonatal Diabetes Mellitus Type 1, Multi Locus Imprinting Disturbance, IUGR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.46 TAF2 Chirag Patel reviewed gene: TAF2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34474177; Phenotypes: Mental retardation, autosomal recessive 40, OMIM # 615599; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4117 TAF2 Chirag Patel reviewed gene: TAF2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34474177; Phenotypes: Mental retardation, autosomal recessive 40, OMIM # 615599; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4117 DDX23 Chirag Patel Classified gene: DDX23 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4117 DDX23 Chirag Patel Gene: ddx23 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4117 DDX23 Chirag Patel Classified gene: DDX23 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4117 DDX23 Chirag Patel Gene: ddx23 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4116 DDX23 Chirag Patel reviewed gene: DDX23: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34050707; Phenotypes: Neurodevelopmental disorder, no OMIM #; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Red cell disorders v0.208 RPL5 Zornitza Stark Marked gene: RPL5 as ready
Red cell disorders v0.208 RPL5 Zornitza Stark Gene: rpl5 has been classified as Green List (High Evidence).
Red cell disorders v0.208 RPL5 Zornitza Stark Phenotypes for gene: RPL5 were changed from Inherited Bone Marrow Failure Syndromes; Diamond Blackfan anemia; 612561 Diamond-Blackfan anemia 6; Diamond-Blackfan anemia 6, 612561; Diamond-Blackfan Anemia 6; 612561 Diamond_Blackfan Anemia 6; Diamond-Blackfan Anemia; DIAMOND-BLACKFAN ANEMIA 6; Diamond_Blackfan Anemia 6 to Diamond-Blackfan anemia 6, MIM# 612561; MONDO:0012937
Red cell disorders v0.207 RPL35A Zornitza Stark Marked gene: RPL35A as ready
Red cell disorders v0.207 RPL35A Zornitza Stark Gene: rpl35a has been classified as Green List (High Evidence).
Red cell disorders v0.207 RPL35A Zornitza Stark Phenotypes for gene: RPL35A were changed from Inherited Bone Marrow Failure Syndromes; DIAMOND-BLACKFAN ANEMIA 5; Diamond-Blackfan anemia 5, 612528; 612528 Diamond-Blackfan anemia 5; Diamond Blackfan anemia; Diamond-Blackfan Anemia; Diamond-Blackfan Anemia 5; 612528 Diamond_Blackfan Anemia 5; Diamond_Blackfan Anemia 5 to Diamond-Blackfan anaemia 5, MIM# 612528
Red cell disorders v0.206 RPL35A Zornitza Stark Publications for gene: RPL35A were set to 18535205
Red cell disorders v0.205 RPL35A Zornitza Stark Tag SV/CNV tag was added to gene: RPL35A.
Red cell disorders v0.205 RPL31 Zornitza Stark Marked gene: RPL31 as ready
Red cell disorders v0.205 RPL31 Zornitza Stark Gene: rpl31 has been classified as Amber List (Moderate Evidence).
Red cell disorders v0.205 RPL31 Zornitza Stark Phenotypes for gene: RPL31 were changed from N/A ? Diamond-Blackfan Anaemia to Diamond Blackfan anaemia
Red cell disorders v0.204 RPL31 Zornitza Stark Classified gene: RPL31 as Amber List (moderate evidence)
Red cell disorders v0.204 RPL31 Zornitza Stark Gene: rpl31 has been classified as Amber List (Moderate Evidence).
Red cell disorders v0.203 RPL27 Zornitza Stark Marked gene: RPL27 as ready
Red cell disorders v0.203 RPL27 Zornitza Stark Gene: rpl27 has been classified as Red List (Low Evidence).
Red cell disorders v0.203 RPL27 Zornitza Stark Phenotypes for gene: RPL27 were changed from Diamond-Blackfan anemia; Diamond-Blackfan anemia 16, 617408 to Diamond-Blackfan anemia 16, MIM# 617408
Red cell disorders v0.202 RPL27 Zornitza Stark Classified gene: RPL27 as Red List (low evidence)
Red cell disorders v0.202 RPL27 Zornitza Stark Gene: rpl27 has been classified as Red List (Low Evidence).
Mendeliome v0.9166 FCGR2B Zornitza Stark Marked gene: FCGR2B as ready
Mendeliome v0.9166 FCGR2B Zornitza Stark Gene: fcgr2b has been classified as Red List (Low Evidence).
Mendeliome v0.9166 FCGR2B Zornitza Stark Phenotypes for gene: FCGR2B were changed from to {Systemic lupus erythematosus, susceptibility to} MIM#152700
Mendeliome v0.9165 FCGR2B Zornitza Stark Publications for gene: FCGR2B were set to
Mendeliome v0.9164 FCGR2B Zornitza Stark Mode of inheritance for gene: FCGR2B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9163 FCGR2B Zornitza Stark Classified gene: FCGR2B as Red List (low evidence)
Mendeliome v0.9163 FCGR2B Zornitza Stark Gene: fcgr2b has been classified as Red List (Low Evidence).
Red cell disorders v0.201 RPS26 Zornitza Stark Marked gene: RPS26 as ready
Red cell disorders v0.201 RPS26 Zornitza Stark Gene: rps26 has been classified as Green List (High Evidence).
Red cell disorders v0.201 RPS26 Zornitza Stark Phenotypes for gene: RPS26 were changed from Diamond-Blackfan anemia 10, 613309; Inherited Bone Marrow Failure Syndromes; Diamond-Blackfan anemia 10; Diamond Blackfan anemia; Diamond-Blackfan Anemia; 613309 Diamond_Blackfan Anemia 10; Diamond_Blackfan Anemia 10; 613309 Diamond-Blackfan anemia 10 to Diamond-Blackfan anemia 10, MIM# 613309; MONDO:0013217
Red cell disorders v0.200 RPS27 Zornitza Stark Marked gene: RPS27 as ready
Red cell disorders v0.200 RPS27 Zornitza Stark Gene: rps27 has been classified as Red List (Low Evidence).
Red cell disorders v0.200 RPS27 Zornitza Stark Phenotypes for gene: RPS27 were changed from Diamond-Blackfan anemia; ?Diamond-Blackfan anemia 17, 617409; 617409 ?Diamond-Blackfan anemia 17, to Diamond-Blackfan anemia 17, MIM# 617409
Red cell disorders v0.199 RPS27 Zornitza Stark Publications for gene: RPS27 were set to 25424902; 23718193
Red cell disorders v0.198 RPS27 Zornitza Stark Classified gene: RPS27 as Red List (low evidence)
Red cell disorders v0.198 RPS27 Zornitza Stark Gene: rps27 has been classified as Red List (Low Evidence).
Red cell disorders v0.197 RPS29 Zornitza Stark Phenotypes for gene: RPS29 were changed from Diamond-Blackfan anemia 13, MIM# 615909 to Diamond-Blackfan anaemia 13, MIM# 615909
Red cell disorders v0.196 RPS29 Zornitza Stark Marked gene: RPS29 as ready
Red cell disorders v0.196 RPS29 Zornitza Stark Gene: rps29 has been classified as Amber List (Moderate Evidence).
Red cell disorders v0.196 RPS29 Zornitza Stark Phenotypes for gene: RPS29 were changed from Diamond-Blackfan anemia 13, 615909; 615909 Diamond-Blackfan anemia 13 to Diamond-Blackfan anemia 13, MIM# 615909
Red cell disorders v0.195 RPS29 Zornitza Stark Classified gene: RPS29 as Amber List (moderate evidence)
Red cell disorders v0.195 RPS29 Zornitza Stark Gene: rps29 has been classified as Amber List (Moderate Evidence).
Red cell disorders v0.194 RPS7 Zornitza Stark Marked gene: RPS7 as ready
Red cell disorders v0.194 RPS7 Zornitza Stark Gene: rps7 has been classified as Green List (High Evidence).
Red cell disorders v0.194 RPS7 Zornitza Stark Phenotypes for gene: RPS7 were changed from Inherited Bone Marrow Failure Syndromes; Diamond Blackfan anemia; Diamond-Blackfan anemia 8, 612563; 612563 Diamond_Blackfan Anemia 8; DIAMOND-BLACKFAN ANEMIA 8; Diamond-Blackfan Anemia; 612563 Diamond-Blackfan anemia 8; Diamond_Blackfan Anemia 8 to Diamond-Blackfan anaemia 8, MIM# 612563; MONDO:0012939
Red cell disorders v0.193 RPS7 Zornitza Stark Publications for gene: RPS7 were set to 19061985; 27882484; 23718193
Red cell disorders v0.192 SBDS Zornitza Stark Marked gene: SBDS as ready
Red cell disorders v0.192 SBDS Zornitza Stark Gene: sbds has been classified as Green List (High Evidence).
Red cell disorders v0.192 SBDS Zornitza Stark Phenotypes for gene: SBDS were changed from 260400 Shwachman-Diamond syndrome; Shwachman-Diamond syndrome to Shwachman-Diamond syndrome, MIM# 260400
Red cell disorders v0.191 SEC23B Zornitza Stark Marked gene: SEC23B as ready
Red cell disorders v0.191 SEC23B Zornitza Stark Gene: sec23b has been classified as Green List (High Evidence).
Red cell disorders v0.191 SEC23B Zornitza Stark Phenotypes for gene: SEC23B were changed from Congenital Dyserythropoietic Anemia; ANEMIA, DYSERYTHROPOIETIC CONGENITAL, TYPE II; 224100 ANEMIA, DYSERYTHROPOIETIC CONGENITAL, TYPE II; Anemia, dyserythropoieticcongenital, type II, 224100; Congenital dyserythropoietic anemia type II; 224100 Congenital dyserythropoietic anaemia type 2 to Dyserythropoietic anaemia, congenital, type II , MIM#224100
Red cell disorders v0.190 SEC23B Zornitza Stark Publications for gene: SEC23B were set to 19561605
Red cell disorders v0.189 SLC19A2 Zornitza Stark Marked gene: SLC19A2 as ready
Red cell disorders v0.189 SLC19A2 Zornitza Stark Gene: slc19a2 has been classified as Green List (High Evidence).
Red cell disorders v0.189 SLC19A2 Zornitza Stark Phenotypes for gene: SLC19A2 were changed from 249270 Thiamine-Responsive Megaloblastic Anemia syndrome; Thiamine-Responsive Megaloblastic Anemia syndrome, 249270; 249270 Thiamine-responsive megaloblastic anemia syndrome to Thiamine-responsive megaloblastic anaemia syndrome, MIM# 249270
Red cell disorders v0.188 SLC25A38 Zornitza Stark Marked gene: SLC25A38 as ready
Red cell disorders v0.188 SLC25A38 Zornitza Stark Gene: slc25a38 has been classified as Green List (High Evidence).
Red cell disorders v0.188 SLC25A38 Zornitza Stark Phenotypes for gene: SLC25A38 were changed from Anemia, sideroblastic, 2, pyridoxine-refractory, 205950; 205950 Pyridoxine refractory sideroblastic anaemia 2; 205950 Anemia, sideroblastic, 2, pyridoxine-refractory to Anaemia, sideroblastic, 2, pyridoxine-refractory, MIM# 205950
Red cell disorders v0.187 XK Zornitza Stark Marked gene: XK as ready
Red cell disorders v0.187 XK Zornitza Stark Gene: xk has been classified as Green List (High Evidence).
Red cell disorders v0.187 XK Zornitza Stark Phenotypes for gene: XK were changed from 300842 McLeod syndrome to McLeod syndrome with or without chronic granulomatous disease MIM# 300842; absence of red blood cell Kx antigen; weak expression of Kell red blood cell antigens; neuroacanthocytosis (peripheral and central nervous systems); cardiovascular abnormalities; myopathy
Red cell disorders v0.186 XK Zornitza Stark Publications for gene: XK were set to 17683354; 11761473
Red cell disorders v0.185 NHP2 Zornitza Stark Marked gene: NHP2 as ready
Red cell disorders v0.185 NHP2 Zornitza Stark Gene: nhp2 has been classified as Red List (Low Evidence).
Red cell disorders v0.185 NHP2 Zornitza Stark Phenotypes for gene: NHP2 were changed from 613987 Dyskeratosis congenita, autosomal recessive 2 to Dyskeratosis congenita, autosomal recessive 2, MIM# 613987
Red cell disorders v0.184 NHP2 Zornitza Stark Publications for gene: NHP2 were set to
Red cell disorders v0.183 NHP2 Zornitza Stark Classified gene: NHP2 as Red List (low evidence)
Red cell disorders v0.183 NHP2 Zornitza Stark Gene: nhp2 has been classified as Red List (Low Evidence).
Red cell disorders v0.182 NHP2 Zornitza Stark changed review comment from: Dyskeratosis congenita is a multisystem disorder caused by defective telomere maintenance. Clinical manifestations include mucocutaneous abnormalities, bone marrow failure, and an increased predisposition to cancer, among other variable features. Three unrelated families reported.; to: Pancytopaenia.
Red cell disorders v0.182 NHP2 Zornitza Stark edited their review of gene: NHP2: Changed rating: RED
Red cell disorders v0.182 RPL18 Zornitza Stark Marked gene: RPL18 as ready
Red cell disorders v0.182 RPL18 Zornitza Stark Gene: rpl18 has been classified as Amber List (Moderate Evidence).
Red cell disorders v0.182 RPL18 Zornitza Stark Phenotypes for gene: RPL18 were changed from Diamond-Blackfan anaemia to Diamond-Blackfan anemia 18, MIM# 618310
Red cell disorders v0.181 RPL18 Zornitza Stark Publications for gene: RPL18 were set to 28280134
Red cell disorders v0.180 RPS28 Zornitza Stark Marked gene: RPS28 as ready
Red cell disorders v0.180 RPS28 Zornitza Stark Gene: rps28 has been classified as Amber List (Moderate Evidence).
Red cell disorders v0.180 RPS28 Zornitza Stark Phenotypes for gene: RPS28 were changed from Diamond Blackfan anemia 15 with mandibulofacial dysostosis, MIM# 606164 to Diamond Blackfan anaemia 15 with mandibulofacial dysostosis, MIM# 606164
Red cell disorders v0.179 RPS28 Zornitza Stark Phenotypes for gene: RPS28 were changed from 606164 Diamond Blackfan anemia 15 with mandibulofacial dysostosis; Diamond Blackfan anemia 15 with mandibulofacial dysostosis, 606164 to Diamond Blackfan anemia 15 with mandibulofacial dysostosis, MIM# 606164
Red cell disorders v0.178 TSR2 Zornitza Stark Marked gene: TSR2 as ready
Red cell disorders v0.178 TSR2 Zornitza Stark Gene: tsr2 has been classified as Red List (Low Evidence).
Red cell disorders v0.178 TSR2 Zornitza Stark Phenotypes for gene: TSR2 were changed from 300946 ?Diamond-Blackfan anemia 14 with mandibulofacial dysostosis; ?Diamond-Blackfan anemia 14 with mandibulofacial dysostosis, 300946 to Diamond-Blackfan anemia 14 with mandibulofacial dysostosis, MIM# 300946
Red cell disorders v0.177 TSR2 Zornitza Stark Classified gene: TSR2 as Red List (low evidence)
Red cell disorders v0.177 TSR2 Zornitza Stark Gene: tsr2 has been classified as Red List (Low Evidence).
Red cell disorders v0.176 ATRX Zornitza Stark Marked gene: ATRX as ready
Red cell disorders v0.176 ATRX Zornitza Stark Gene: atrx has been classified as Green List (High Evidence).
Red cell disorders v0.176 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from 301040 Alpha-thalassemia/mental retardation syndrome to Alpha-thalassaemia/mental retardation syndrome, MIM# 301040
Red cell disorders v0.175 ATRX Zornitza Stark Publications for gene: ATRX were set to 19444090; 17579672; 11449489
Red cell disorders v0.174 ATRX Zornitza Stark Mode of inheritance for gene: ATRX was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Red cell disorders v0.173 ATRX Zornitza Stark Classified gene: ATRX as Green List (high evidence)
Red cell disorders v0.173 ATRX Zornitza Stark Gene: atrx has been classified as Green List (High Evidence).
Red cell disorders v0.172 ATRX Zornitza Stark reviewed gene: ATRX: Rating: GREEN; Mode of pathogenicity: None; Publications: 7697714; Phenotypes: Alpha-thalassaemia/mental retardation syndrome, MIM# 301040; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Red cell disorders v0.172 DKC1 Zornitza Stark Marked gene: DKC1 as ready
Red cell disorders v0.172 DKC1 Zornitza Stark Gene: dkc1 has been classified as Red List (Low Evidence).
Red cell disorders v0.172 DKC1 Zornitza Stark Phenotypes for gene: DKC1 were changed from 305000 Dyskeratosis congenita, X-linked to Dyskeratosis congenita, X-linked 305000; Hoyeraal-Hreidarsson Syndrome
Red cell disorders v0.171 DKC1 Zornitza Stark Publications for gene: DKC1 were set to
Red cell disorders v0.170 DKC1 Zornitza Stark changed review comment from: Dyskeratosis congenita is classically defined by the triad of abnormal skin pigmentation, nail dystrophy, and leukoplakia of the oral mucosa. It is characterized by short telomeres. Progressive bone marrow failure occurs in over 80% of cases and is the main cause of early mortality. The phenotype is highly variable, and affected individuals may have multiple additional features, including pulmonary fibrosis, liver cirrhosis, premature hair loss and/or graying, osteoporosis, atresia of the lacrimal ducts, and learning difficulties. Males may have testicular atrophy. Predisposition to malignancy is an important feature.

Hoyeraal-Hreidarsson syndrome (HHS) refers to a clinically severe variant of DKC that is characterized by multisystem involvement and early onset in utero. Patients with HHS show intrauterine growth retardation, microcephaly, delayed development, and bone marrow failure resulting in immunodeficiency, cerebellar hypoplasia, and sometimes enteropathy. Death often occurs in childhood.

PMID: 25940403, at least 13 of the variants associated with dyskeratosis congenita were also reported to cause HHS: P10L, I38T, T66A, T67I, H68Q, H68Y, S121G, R158W, K314R, A353V, R378Q, A386T and IVS12+1, so NOT only variants in exon 11. Two mutations were only found in HH, T49M and S304N.; to: Pancytopaenia rather than a red cell disorder.
Red cell disorders v0.170 DKC1 Zornitza Stark edited their review of gene: DKC1: Changed rating: RED
Red cell disorders v0.170 Zornitza Stark removed gene:HBE1 from the panel
Red cell disorders v0.169 SF3B1 Zornitza Stark Marked gene: SF3B1 as ready
Red cell disorders v0.169 SF3B1 Zornitza Stark Gene: sf3b1 has been classified as Red List (Low Evidence).
Red cell disorders v0.169 SF3B1 Zornitza Stark Phenotypes for gene: SF3B1 were changed from 605590 Refractory anaemia with ring sideroblasts to Myelodysplastic syndrome, somatic MIM# 614286
Red cell disorders v0.168 SF3B1 Zornitza Stark Mode of inheritance for gene: SF3B1 was changed from Unknown to Other
Red cell disorders v0.167 SF3B1 Zornitza Stark Tag somatic tag was added to gene: SF3B1.
Mendeliome v0.9162 FCGR2B Paul De Fazio reviewed gene: FCGR2B: Rating: RED; Mode of pathogenicity: None; Publications: 12115230, 15153543, 20385827; Phenotypes: {Systemic lupus erythematosus, susceptibility to} MIM#152700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.9162 GPX1 Zornitza Stark Marked gene: GPX1 as ready
Mendeliome v0.9162 GPX1 Zornitza Stark Gene: gpx1 has been classified as Red List (Low Evidence).
Mendeliome v0.9162 GPX1 Zornitza Stark gene: GPX1 was added
gene: GPX1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: GPX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPX1 were set to 1131421; 476008; 5766310; 2492138
Phenotypes for gene: GPX1 were set to Haemolytic anaemia due to glutathione peroxidase deficiency MIM#614164
Review for gene: GPX1 was set to RED
Added comment: No individuals reported with GPX1 variants identified as the cause of Haemolytic anaemia due to glutathione peroxidase deficiency. Multiple papers report a number of cases of Haemolytic anaemia due to glutathione peroxidase deficiency, however there is no defined link or variant to GPX1 (PMID: 5766310. PMID: 1131421, PMID: 2492138, PMID: 476008)

Overall, lowered glutathione peroxidase activity has been observed in a number of individuals with haemolytic anaemia however the evidence for a cause-and-effect relationship between the enzyme deficiency and the presenting anaemia is not evident.
Sources: Expert Review
Red cell disorders v0.167 GPX1 Zornitza Stark Marked gene: GPX1 as ready
Red cell disorders v0.167 GPX1 Zornitza Stark Gene: gpx1 has been classified as Red List (Low Evidence).
Red cell disorders v0.167 GPX1 Zornitza Stark Phenotypes for gene: GPX1 were changed from 614164 Hemolytic anemia due to glutathione peroxidase deficiency to Haemolytic anaemia due to glutathione peroxidase deficiency MIM#614164
Red cell disorders v0.166 GPX1 Zornitza Stark Publications for gene: GPX1 were set to 1131421
Mendeliome v0.9161 CYP51A1 Bryony Thompson Mode of inheritance for gene: CYP51A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9160 CYP51A1 Bryony Thompson reviewed gene: CYP51A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22935719, 26622071, 27878435, 25148791; Phenotypes: Congenital cataract, infantile liver disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cataract v0.289 CYP51A1 Bryony Thompson Phenotypes for gene: CYP51A1 were changed from to Congenital cataract; infantile liver disease
Cataract v0.288 CYP51A1 Bryony Thompson Publications for gene: CYP51A1 were set to
Cataract v0.287 CYP51A1 Bryony Thompson Marked gene: CYP51A1 as ready
Cataract v0.287 CYP51A1 Bryony Thompson Gene: cyp51a1 has been classified as Green List (High Evidence).
Cataract v0.287 CYP51A1 Bryony Thompson reviewed gene: CYP51A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22935719, 26622071, 27878435, 25148791; Phenotypes: Congenital cataract, infantile liver disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9160 CYB5A Zornitza Stark Marked gene: CYB5A as ready
Mendeliome v0.9160 CYB5A Zornitza Stark Gene: cyb5a has been classified as Green List (High Evidence).
Mendeliome v0.9160 CYB5A Zornitza Stark Phenotypes for gene: CYB5A were changed from to Methemoglobinaemia and ambiguous genitalia, MIM# 250790
Mendeliome v0.9159 CYB5A Zornitza Stark Publications for gene: CYB5A were set to
Mendeliome v0.9158 CYB5A Zornitza Stark Mode of inheritance for gene: CYB5A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9157 CYB5A Zornitza Stark reviewed gene: CYB5A: Rating: GREEN; Mode of pathogenicity: None; Publications: 22170710, 32051920; Phenotypes: Methemoglobinemia and ambiguous genitalia 250790; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Red cell disorders v0.165 CYB5A Zornitza Stark Marked gene: CYB5A as ready
Red cell disorders v0.165 CYB5A Zornitza Stark Gene: cyb5a has been classified as Amber List (Moderate Evidence).
Red cell disorders v0.165 CYB5A Zornitza Stark Phenotypes for gene: CYB5A were changed from 250790 Methemoglobinemia and ambiguous genitalia to Methemoglobinaemia and ambiguous genitalia MIM#250790
Red cell disorders v0.164 CYB5A Zornitza Stark Publications for gene: CYB5A were set to 8168836; 20080843
Red cell disorders v0.163 CYB5A Zornitza Stark Classified gene: CYB5A as Amber List (moderate evidence)
Red cell disorders v0.163 CYB5A Zornitza Stark Gene: cyb5a has been classified as Amber List (Moderate Evidence).
Red cell disorders v0.162 FTCD Zornitza Stark Marked gene: FTCD as ready
Red cell disorders v0.162 FTCD Zornitza Stark Gene: ftcd has been classified as Amber List (Moderate Evidence).
Red cell disorders v0.162 FTCD Zornitza Stark Phenotypes for gene: FTCD were changed from 229100 Glutamate formiminotransferase deficiency to Glutamate formiminotransferase deficiency MIM# 229100
Red cell disorders v0.161 FTCD Zornitza Stark Publications for gene: FTCD were set to 12815595
Red cell disorders v0.160 FTCD Zornitza Stark Classified gene: FTCD as Amber List (moderate evidence)
Red cell disorders v0.160 FTCD Zornitza Stark Gene: ftcd has been classified as Amber List (Moderate Evidence).
Red cell disorders v0.159 GPX1 Danielle Ariti reviewed gene: GPX1: Rating: RED; Mode of pathogenicity: None; Publications: 1131421, 476008, 5766310, 2492138; Phenotypes: Haemolytic anaemia due to glutathione peroxidase deficiency MIM#614164; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Red cell disorders v0.159 SH2B3 Zornitza Stark Marked gene: SH2B3 as ready
Red cell disorders v0.159 SH2B3 Zornitza Stark Gene: sh2b3 has been classified as Amber List (Moderate Evidence).
Red cell disorders v0.159 SH2B3 Zornitza Stark Classified gene: SH2B3 as Amber List (moderate evidence)
Red cell disorders v0.159 SH2B3 Zornitza Stark Gene: sh2b3 has been classified as Amber List (Moderate Evidence).
Red cell disorders v0.158 SH2B3 Zornitza Stark gene: SH2B3 was added
gene: SH2B3 was added to Red cell disorders. Sources: Expert Review
somatic tags were added to gene: SH2B3.
Mode of inheritance for gene: SH2B3 was set to Other
Publications for gene: SH2B3 were set to 34349782; 23812944; 20843259
Phenotypes for gene: SH2B3 were set to Erythrocytosis, somatic, MIM# 133100
Mode of pathogenicity for gene: SH2B3 was set to Other
Review for gene: SH2B3 was set to AMBER
Added comment: Limited reports, variants appear to be somatic.
Sources: Expert Review
Red cell disorders v0.157 JAK2 Zornitza Stark Marked gene: JAK2 as ready
Red cell disorders v0.157 JAK2 Zornitza Stark Gene: jak2 has been classified as Amber List (Moderate Evidence).
Red cell disorders v0.157 JAK2 Zornitza Stark Classified gene: JAK2 as Amber List (moderate evidence)
Red cell disorders v0.157 JAK2 Zornitza Stark Gene: jak2 has been classified as Amber List (Moderate Evidence).
Red cell disorders v0.156 JAK2 Zornitza Stark gene: JAK2 was added
gene: JAK2 was added to Red cell disorders. Sources: Expert Review
somatic tags were added to gene: JAK2.
Mode of inheritance for gene: JAK2 was set to Other
Publications for gene: JAK2 were set to 27389715
Phenotypes for gene: JAK2 were set to Erythrocytosis, somatic, 133100
Mode of pathogenicity for gene: JAK2 was set to Other
Review for gene: JAK2 was set to AMBER
Added comment: There is limited evidence to support an association of JAK2 variants with hereditary/congenital erythrocytosis. Typically, variants are somatic/acquired; and to date, only one report has described a patient with germline compound het variants (p.E846D and p.R1063H) in JAK2, who exhibited polyclonal erythrocytosis and megakaryocytic atypia but normal platelet number (PMID:27389715).

GoF somatic variants in this gene are also associated with polycythaemia vera (PV), particularly p.V617F, but also with reports of some familial clustering due to inheritance of the JAK2 46/1 predisposition haplotype.

Amber rating due to the somatic nature of variants.
Sources: Expert Review
Red cell disorders v0.155 VHL Zornitza Stark Marked gene: VHL as ready
Red cell disorders v0.155 VHL Zornitza Stark Gene: vhl has been classified as Green List (High Evidence).
Red cell disorders v0.155 VHL Zornitza Stark Classified gene: VHL as Green List (high evidence)
Red cell disorders v0.155 VHL Zornitza Stark Gene: vhl has been classified as Green List (High Evidence).
Red cell disorders v0.154 VHL Zornitza Stark gene: VHL was added
gene: VHL was added to Red cell disorders. Sources: Expert list
Mode of inheritance for gene: VHL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VHL were set to 12844285; 21454469; 24729484; 23403324
Phenotypes for gene: VHL were set to Erythrocytosis, familial, 2, MIM# 263400
Mode of pathogenicity for gene: VHL was set to Other
Review for gene: VHL was set to GREEN
Added comment: Well established gene-disease association. Bi-allelic missense variants, postulated to be hypomorphic.

Note mono-allelic variants associated with Von Hippel Lindau syndrome.
Sources: Expert list
Red cell disorders v0.153 SF3B1 Danielle Ariti reviewed gene: SF3B1: Rating: RED; Mode of pathogenicity: Other; Publications: 21995386, 21909114; Phenotypes: Myelodysplastic syndrome, somatic MIM# 614286; Mode of inheritance: Other
Red cell disorders v0.153 CYB5A Danielle Ariti reviewed gene: CYB5A: Rating: AMBER; Mode of pathogenicity: None; Publications: 22170710, 20080843, 32051920, 3951505; Phenotypes: Methemoglobinaemia and ambiguous genitalia MIM#250790; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Red cell disorders v0.153 EPOR Zornitza Stark Marked gene: EPOR as ready
Red cell disorders v0.153 EPOR Zornitza Stark Gene: epor has been classified as Green List (High Evidence).
Red cell disorders v0.153 EPOR Zornitza Stark Classified gene: EPOR as Green List (high evidence)
Red cell disorders v0.153 EPOR Zornitza Stark Gene: epor has been classified as Green List (High Evidence).
Red cell disorders v0.152 EPOR Zornitza Stark gene: EPOR was added
gene: EPOR was added to Red cell disorders. Sources: Expert list
Mode of inheritance for gene: EPOR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EPOR were set to 8506290; 9292543; 30507031; 33061762
Phenotypes for gene: EPOR were set to [Erythrocytosis, familial, 1], MIM# 133100
Review for gene: EPOR was set to GREEN
Added comment: Well established gene-disease association.
Sources: Expert list
Red cell disorders v0.151 FTCD Danielle Ariti reviewed gene: FTCD: Rating: AMBER; Mode of pathogenicity: None; Publications: 29178637, 30740726, 5301410; Phenotypes: Glutamate formiminotransferase deficiency MIM# 229100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Palmoplantar Keratoderma and Erythrokeratoderma v0.107 ALOX12B Zornitza Stark Marked gene: ALOX12B as ready
Palmoplantar Keratoderma and Erythrokeratoderma v0.107 ALOX12B Zornitza Stark Gene: alox12b has been classified as Green List (High Evidence).
Palmoplantar Keratoderma and Erythrokeratoderma v0.107 ALOX12B Zornitza Stark Phenotypes for gene: ALOX12B were changed from to Ichthyosis, congenital, autosomal recessive 2, MIM# 242100
Palmoplantar Keratoderma and Erythrokeratoderma v0.106 ALOX12B Zornitza Stark Mode of inheritance for gene: ALOX12B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Palmoplantar Keratoderma and Erythrokeratoderma v0.105 ALOX12B Zornitza Stark reviewed gene: ALOX12B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ichthyosis, congenital, autosomal recessive 2, MIM# 242100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9157 COL14A1 Zornitza Stark Marked gene: COL14A1 as ready
Mendeliome v0.9157 COL14A1 Zornitza Stark Gene: col14a1 has been classified as Red List (Low Evidence).
Mendeliome v0.9157 COL14A1 Zornitza Stark gene: COL14A1 was added
gene: COL14A1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: COL14A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL14A1 were set to 22972947
Phenotypes for gene: COL14A1 were set to Punctate palmoplantar keratoderma type 1B
Review for gene: COL14A1 was set to RED
Added comment: 4 affected individuals and 2 unaffected controls from one Chinese PPPK family where disease locus was mapped at 8q24.13-8q24.21 by previous linkage analysis. Exome sequencing analysis identified a heterozygous variant in COL14A1 gene (c.4505C>T (p.Pro1502Leu)). The variant was shared by 4 affected individuals, but not 2 controls of the family. Sanger sequencing confirmed this variant in another four cases from this family. Variant was absent in the normal controls of this family as well as 676 unrelated normal controls and 781 patients with other disease. The missense substitution occurs at a highly conserved amino acid residue across multiple species.
Sources: Expert Review
Palmoplantar Keratoderma and Erythrokeratoderma v0.105 COL14A1 Zornitza Stark Marked gene: COL14A1 as ready
Palmoplantar Keratoderma and Erythrokeratoderma v0.105 COL14A1 Zornitza Stark Gene: col14a1 has been classified as Red List (Low Evidence).
Palmoplantar Keratoderma and Erythrokeratoderma v0.105 SMARCAD1 Zornitza Stark Phenotypes for gene: SMARCAD1 were changed from Basan syndrome (MIM#129200) to Basan syndrome, MIM#129200; Huriez syndrome, OMIM #181600
Palmoplantar Keratoderma and Erythrokeratoderma v0.104 NLRP1 Zornitza Stark Marked gene: NLRP1 as ready
Palmoplantar Keratoderma and Erythrokeratoderma v0.104 NLRP1 Zornitza Stark Gene: nlrp1 has been classified as Green List (High Evidence).
Palmoplantar Keratoderma and Erythrokeratoderma v0.104 Chirag Patel Panel types changed to Victorian Clinical Genetics Services; Genetic Health Queensland; Royal Melbourne Hospital; Rare Disease
Palmoplantar Keratoderma and Erythrokeratoderma v0.103 NLRP1 Chirag Patel Classified gene: NLRP1 as Green List (high evidence)
Palmoplantar Keratoderma and Erythrokeratoderma v0.103 NLRP1 Chirag Patel Gene: nlrp1 has been classified as Green List (High Evidence).
Palmoplantar Keratoderma and Erythrokeratoderma v0.102 NLRP1 Chirag Patel gene: NLRP1 was added
gene: NLRP1 was added to Palmoplantar Keratoderma and Erythrokeratoderma. Sources: Literature
Mode of inheritance for gene: NLRP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NLRP1 were set to PMID: 27662089
Phenotypes for gene: NLRP1 were set to Palmoplantar carcinoma, multiple self-healing, OMIM # 615225
Review for gene: NLRP1 was set to GREEN
Added comment: Multiple self-healing palmoplantar carcinoma (MSPC) is characterised by recurrent keratoacanthomas in palmoplantar skin and conjunctival and corneal epithelia. Patients experience a high susceptibility to malignant squamous cell carcinoma.

Zhong et al. (2016) reported 3 families with variants in NLRP1
a) Affected mother and son with MSPC from a Caucasian French family. Whole exome sequencing (+ Sanger sequencing) identified a heterozygous missense mutation in NLRP1 gene (M77T), that appeared de novo in the mother and segregated with disease in the family. The variant was not found in 672 controls or 61 exome-sequenced subjects' DNA.
b) Large 5-generation Tunisian family segregating autosomal dominant MSPC. Whole exome sequencing identified a heterozygous missense mutation in exon 1 of NLRP1 gene (A54T), that segregated with disease in 16 family members.
c) 4-generation kindred with MSPC. Sanger sequencing of NLRP1 exon 1 identified heterozygosity for a missense mutation (A66V, that segregated with disease in the family.
d) 2 sibs in a consanguineous family with features of MSPC, with homozygous in-frame deletion in NLRP1 gene.
Functional analysis demonstrated that all 3 MSPC-associated missense mutations are gain-of-function variants that cause increased inflammasome activation.
Sources: Literature
Palmoplantar Keratoderma and Erythrokeratoderma v0.101 SMARCAD1 Chirag Patel Classified gene: SMARCAD1 as Green List (high evidence)
Palmoplantar Keratoderma and Erythrokeratoderma v0.101 SMARCAD1 Chirag Patel Gene: smarcad1 has been classified as Green List (High Evidence).
Palmoplantar Keratoderma and Erythrokeratoderma v0.100 SMARCAD1 Chirag Patel reviewed gene: SMARCAD1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29409814; Phenotypes: Huriez syndrome, OMIM #181600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Palmoplantar Keratoderma and Erythrokeratoderma v0.100 COL14A1 Chirag Patel gene: COL14A1 was added
gene: COL14A1 was added to Palmoplantar Keratoderma and Erythrokeratoderma. Sources: Literature
Mode of inheritance for gene: COL14A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL14A1 were set to PMID: 22972947
Phenotypes for gene: COL14A1 were set to Punctate palmoplantar keratoderma type 1B
Review for gene: COL14A1 was set to RED
Added comment: 4 affected individuals and 2 unaffected controls from one Chinese PPPK family where disease locus was mapped at 8q24.13-8q24.21 by previous linkage analysis. Exome sequencing analysis identified a heterozygous variant in COL14A1 gene (c.4505C>T (p.Pro1502Leu)). The variant was shared by 4 affected individuals, but not 2 controls of the family. Sanger sequencing confirmed this variant in another four cases from this family. Variant was absent in the normal controls of this family as well as 676 unrelated normal controls and 781 patients with other disease. The missense substitution occurs at a highly conserved amino acid residue across multiple species.
Sources: Literature
Red cell disorders v0.151 EPO Zornitza Stark Marked gene: EPO as ready
Red cell disorders v0.151 EPO Zornitza Stark Gene: epo has been classified as Green List (High Evidence).
Red cell disorders v0.151 EPO Zornitza Stark Classified gene: EPO as Green List (high evidence)
Red cell disorders v0.151 EPO Zornitza Stark Gene: epo has been classified as Green List (High Evidence).
Red cell disorders v0.150 EPO Zornitza Stark gene: EPO was added
gene: EPO was added to Red cell disorders. Sources: Expert list
Mode of inheritance for gene: EPO was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EPO were set to 27651169; 29514032; 32130275; 20700488; 30507031; 28283061
Phenotypes for gene: EPO were set to Erythrocytosis, familial, 5, MIM# 617907; Diamond-Blackfan anaemia-like, MIM# 617911
Review for gene: EPO was set to GREEN
Added comment: More than 5 unrelated families reported, though note one paper has been retracted.

Single family with bi-allelic variants and a DBA phenotype.
Sources: Expert list
Red cell disorders v0.149 EPAS1 Zornitza Stark Marked gene: EPAS1 as ready
Red cell disorders v0.149 EPAS1 Zornitza Stark Gene: epas1 has been classified as Green List (High Evidence).
Red cell disorders v0.149 EPAS1 Zornitza Stark Classified gene: EPAS1 as Green List (high evidence)
Red cell disorders v0.149 EPAS1 Zornitza Stark Gene: epas1 has been classified as Green List (High Evidence).
Red cell disorders v0.148 EPAS1 Zornitza Stark gene: EPAS1 was added
gene: EPAS1 was added to Red cell disorders. Sources: Expert list
Mode of inheritance for gene: EPAS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EPAS1 were set to 18184961; 18378852; 22367913; 18650473
Phenotypes for gene: EPAS1 were set to Erythrocytosis, familial, 4, MIM# 611783
Mode of pathogenicity for gene: EPAS1 was set to Other
Review for gene: EPAS1 was set to GREEN
Added comment: Most mutations are gain-of-function missense variants in exon 12, but variants in exon 9 have also been described, in association with paraganglioma.
Sources: Expert list
Mendeliome v0.9156 EGLN1 Zornitza Stark Marked gene: EGLN1 as ready
Mendeliome v0.9156 EGLN1 Zornitza Stark Gene: egln1 has been classified as Green List (High Evidence).
Mendeliome v0.9156 EGLN1 Zornitza Stark Phenotypes for gene: EGLN1 were changed from to Erythrocytosis, familial, 3, MIM# 609820
Mendeliome v0.9155 EGLN1 Zornitza Stark Publications for gene: EGLN1 were set to
Mendeliome v0.9154 EGLN1 Zornitza Stark Mode of inheritance for gene: EGLN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9153 EGLN1 Zornitza Stark reviewed gene: EGLN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19092153, 16407130, 17579185; Phenotypes: Erythrocytosis, familial, 3, MIM# 609820; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Red cell disorders v0.147 EGLN1 Zornitza Stark Marked gene: EGLN1 as ready
Red cell disorders v0.147 EGLN1 Zornitza Stark Gene: egln1 has been classified as Green List (High Evidence).
Red cell disorders v0.147 EGLN1 Zornitza Stark Classified gene: EGLN1 as Green List (high evidence)
Red cell disorders v0.147 EGLN1 Zornitza Stark Gene: egln1 has been classified as Green List (High Evidence).
Red cell disorders v0.146 EGLN1 Zornitza Stark gene: EGLN1 was added
gene: EGLN1 was added to Red cell disorders. Sources: Expert list
Mode of inheritance for gene: EGLN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EGLN1 were set to 19092153; 16407130; 17579185
Phenotypes for gene: EGLN1 were set to Erythrocytosis, familial, 3, MIM# 609820
Review for gene: EGLN1 was set to GREEN
Added comment: At least 3 unrelated families reported.
Sources: Expert list
Red cell disorders v0.145 BPGM Zornitza Stark Marked gene: BPGM as ready
Red cell disorders v0.145 BPGM Zornitza Stark Gene: bpgm has been classified as Amber List (Moderate Evidence).
Red cell disorders v0.145 BPGM Zornitza Stark Classified gene: BPGM as Amber List (moderate evidence)
Red cell disorders v0.145 BPGM Zornitza Stark Gene: bpgm has been classified as Amber List (Moderate Evidence).
Red cell disorders v0.144 BPGM Zornitza Stark gene: BPGM was added
gene: BPGM was added to Red cell disorders. Sources: Expert list
Mode of inheritance for gene: BPGM was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: BPGM were set to 1421379; 27651169; 25015942
Phenotypes for gene: BPGM were set to Erythrocytosis, familial, 8, MIM# 222800
Review for gene: BPGM was set to AMBER
Added comment: Mixture of mono-allelic and bi-allelic variants reported, MOI uncertain.
Sources: Expert list
Holoprosencephaly and septo-optic dysplasia v1.2 RAD21 Zornitza Stark Publications for gene: RAD21 were set to 31334757
Holoprosencephaly and septo-optic dysplasia v1.1 RAD21 Arina Puzriakova reviewed gene: RAD21: Rating: ; Mode of pathogenicity: None; Publications: 32696056; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.9153 FGFR2 Zornitza Stark Marked gene: FGFR2 as ready
Mendeliome v0.9153 FGFR2 Zornitza Stark Gene: fgfr2 has been classified as Green List (High Evidence).
Mendeliome v0.9153 FGFR2 Zornitza Stark Phenotypes for gene: FGFR2 were changed from to Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis,MIM# 207410; Apert syndrome, MIM# 101200; Beare-Stevenson cutis gyrata syndrome, MIM# 123790; Bent bone dysplasia syndrome, MIM# 614592; Craniofacial-skeletal-dermatologic dysplasia, MIM# 101600; Craniosynostosis, nonspecific; Crouzon syndrome , MIM#123500; Jackson-Weiss syndrome,MIM# 123150; LADD syndrome, MIM# 149730; Pfeiffer syndrome,MIM# 101600; Saethre-Chotzen syndrome 101400
Mendeliome v0.9152 FGFR2 Zornitza Stark Publications for gene: FGFR2 were set to
Mendeliome v0.9151 FGFR2 Zornitza Stark Mode of inheritance for gene: FGFR2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9150 SLC4A1 Zornitza Stark Marked gene: SLC4A1 as ready
Mendeliome v0.9150 SLC4A1 Zornitza Stark Gene: slc4a1 has been classified as Green List (High Evidence).
Mendeliome v0.9150 SLC4A1 Zornitza Stark Phenotypes for gene: SLC4A1 were changed from to Cryohydrocytosis MIM# 185020; Distal renal tubular acidosis 4 with haemolytic anaemia MIM# 611590; Ovalocytosis, SA type MIM# 166900; Spherocytosis, type 4 MIM# 612653; Distal renal tubular acidosis 1 MIM# 179800
Mendeliome v0.9149 SLC4A1 Zornitza Stark Publications for gene: SLC4A1 were set to
Mendeliome v0.9148 SLC4A1 Zornitza Stark Mode of inheritance for gene: SLC4A1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9147 FGFR2 Chern Lim reviewed gene: FGFR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29848297, 32879300, 27323706; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.9147 SLC4A1 Danielle Ariti reviewed gene: SLC4A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16227998, 15211439, 7949112, 8640229, 16227998, 8640229, 16227998, 33881640, 32632909; Phenotypes: Cryohydrocytosis MIM# 185020, Distal renal tubular acidosis 4 with haemolytic anaemia MIM# 611590, Ovalocytosis, SA type MIM# 166900, Spherocytosis, type 4 MIM# 612653, Distal renal tubular acidosis 1 MIM# 179800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Red cell disorders v0.143 TRNT1 Zornitza Stark Marked gene: TRNT1 as ready
Red cell disorders v0.143 TRNT1 Zornitza Stark Gene: trnt1 has been classified as Green List (High Evidence).
Red cell disorders v0.143 TRNT1 Zornitza Stark Phenotypes for gene: TRNT1 were changed from sideroblastic anaemia; 616084 Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay to Sideroblastic anaemia with B-cell immunodeficiency, periodic fevers, and developmental delay, MIM# 616084
Red cell disorders v0.142 TRNT1 Zornitza Stark Publications for gene: TRNT1 were set to
Red cell disorders v0.141 TRNT1 Zornitza Stark reviewed gene: TRNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25193871, 23553769, 29170023, 27389523; Phenotypes: Sideroblastic anaemia with B-cell immunodeficiency, periodic fevers, and developmental delay, MIM# 616084; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Metal Metabolism Disorders v0.27 STEAP3 Zornitza Stark Marked gene: STEAP3 as ready
Metal Metabolism Disorders v0.27 STEAP3 Zornitza Stark Gene: steap3 has been classified as Red List (Low Evidence).
Metal Metabolism Disorders v0.27 STEAP3 Zornitza Stark Phenotypes for gene: STEAP3 were changed from 615234 ?Anemia, hypochromic microcytic, with iron overload 2 to Anaemia, hypochromic microcytic, with iron overload 2 MIM# 615234
Metal Metabolism Disorders v0.26 STEAP3 Zornitza Stark Publications for gene: STEAP3 were set to 22031863
Metal Metabolism Disorders v0.25 STEAP3 Zornitza Stark Mode of inheritance for gene: STEAP3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Metal Metabolism Disorders v0.24 STEAP3 Zornitza Stark Classified gene: STEAP3 as Red List (low evidence)
Metal Metabolism Disorders v0.24 STEAP3 Zornitza Stark Gene: steap3 has been classified as Red List (Low Evidence).
Metal Metabolism Disorders v0.23 STEAP3 Zornitza Stark reviewed gene: STEAP3: Rating: RED; Mode of pathogenicity: None; Publications: 22031863, 25515317, 26675350; Phenotypes: Anaemia, hypochromic microcytic, with iron overload 2 MIM# 615234; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9147 STEAP3 Zornitza Stark Phenotypes for gene: STEAP3 were changed from Anemia, hypochromic microcytic, with iron overload 2, MIM# 615234 to Anaemia, hypochromic microcytic, with iron overload 2, MIM# 615234
Mendeliome v0.9146 STEAP3 Zornitza Stark Publications for gene: STEAP3 were set to 22031863; 25515317
Mendeliome v0.9145 STEAP3 Zornitza Stark Classified gene: STEAP3 as Red List (low evidence)
Mendeliome v0.9145 STEAP3 Zornitza Stark Gene: steap3 has been classified as Red List (Low Evidence).
Mendeliome v0.9144 STEAP3 Zornitza Stark changed review comment from: Single family reported. Three affected sibs, variant inherited from unaffected father. Some supportive functional evidence.; to: Single family reported. Three affected sibs, variant inherited from unaffected father. Some supportive functional evidence.

Conflicting evidence (PMID 26675350): Large Chinese study (of normal and α-thalassemia subjects) investigated the prevalence of STEAP3 mutations in humans and their physiologic consequences. Discovered a relatively high prevalence of potentially harmful recessive alleles. However, whilst the identified STEAP3 mutations exhibited impaired ferrireductase activity in vitro, they had little or no effect on erythrocyte phenotypes
Mendeliome v0.9144 STEAP3 Zornitza Stark edited their review of gene: STEAP3: Changed rating: RED; Changed publications: 22031863, 25515317, 26675350; Changed phenotypes: Anaemia, hypochromic microcytic, with iron overload 2, MIM# 615234
Red cell disorders v0.141 STEAP3 Zornitza Stark Marked gene: STEAP3 as ready
Red cell disorders v0.141 STEAP3 Zornitza Stark Gene: steap3 has been classified as Red List (Low Evidence).
Red cell disorders v0.141 STEAP3 Zornitza Stark Phenotypes for gene: STEAP3 were changed from hypochromic anaemia to Anaemia, hypochromic microcytic, with iron overload 2 MIM# 615234
Red cell disorders v0.140 STEAP3 Zornitza Stark Publications for gene: STEAP3 were set to
Red cell disorders v0.139 STEAP3 Zornitza Stark Mode of inheritance for gene: STEAP3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Red cell disorders v0.138 STEAP3 Zornitza Stark Classified gene: STEAP3 as Red List (low evidence)
Red cell disorders v0.138 STEAP3 Zornitza Stark Gene: steap3 has been classified as Red List (Low Evidence).
Red cell disorders v0.137 PGK1 Zornitza Stark Marked gene: PGK1 as ready
Red cell disorders v0.137 PGK1 Zornitza Stark Gene: pgk1 has been classified as Green List (High Evidence).
Red cell disorders v0.137 PGK1 Zornitza Stark Phenotypes for gene: PGK1 were changed from 300653 Phosphoglycerate kinase 1 deficiency to Phosphoglycerate kinase 1 deficiency MIM# 300653
Red cell disorders v0.136 PGK1 Zornitza Stark Publications for gene: PGK1 were set to 16740138; 6412025
Red cell disorders v0.135 PGK1 Zornitza Stark Classified gene: PGK1 as Green List (high evidence)
Red cell disorders v0.135 PGK1 Zornitza Stark Gene: pgk1 has been classified as Green List (High Evidence).
Red cell disorders v0.134 LARS2 Zornitza Stark Marked gene: LARS2 as ready
Red cell disorders v0.134 LARS2 Zornitza Stark Gene: lars2 has been classified as Amber List (Moderate Evidence).
Red cell disorders v0.134 LARS2 Zornitza Stark Phenotypes for gene: LARS2 were changed from hydrops/sideroblastic anaemia to Hydrops, lactic acidosis, and sideroblastic anaemia MIM# 617021
Red cell disorders v0.133 LARS2 Zornitza Stark Publications for gene: LARS2 were set to
Red cell disorders v0.132 LARS2 Zornitza Stark Mode of inheritance for gene: LARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Red cell disorders v0.131 SLC4A1 Zornitza Stark Marked gene: SLC4A1 as ready
Red cell disorders v0.131 SLC4A1 Zornitza Stark Gene: slc4a1 has been classified as Green List (High Evidence).
Red cell disorders v0.131 SLC4A1 Zornitza Stark Phenotypes for gene: SLC4A1 were changed from 166900 Ovalocytosis, SA type, 185020 Cryohydrocytosis; RBC membrane abnormality; 166900 Ovalocytosis, SA type; Haemolytic Anemia; Cryohydrocytosis,185020; 612653 Spherocytosis, type 4; Ovalocytosis, SA type, 166900; Spherocytosis, type 4, 612653 to Cryohydrocytosis MIM# 185020; Distal renal tubular acidosis 4 with haemolytic anaemia MIM# 611590; Ovalocytosis, SA type MIM# 166900; Spherocytosis, type 4 MIM# 612653
Red cell disorders v0.130 SLC4A1 Zornitza Stark Publications for gene: SLC4A1 were set to 1722314
Red cell disorders v0.129 SLC4A1 Zornitza Stark Mode of inheritance for gene: SLC4A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Red cell disorders v0.128 STEAP3 Danielle Ariti reviewed gene: STEAP3: Rating: RED; Mode of pathogenicity: None; Publications: 22031863, 25515317, 26675350; Phenotypes: Anaemia, hypochromic microcytic, with iron overload 2 MIM# 615234; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Red cell disorders v0.128 PGK1 Danielle Ariti reviewed gene: PGK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28580215, 20151463; Phenotypes: Phosphoglycerate kinase 1 deficiency MIM# 300653; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Red cell disorders v0.128 LARS2 Danielle Ariti reviewed gene: LARS2: Rating: AMBER; Mode of pathogenicity: None; Publications: 26537577, 32442335; Phenotypes: Hydrops, lactic acidosis, and sideroblastic anaemia MIM# 617021; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Red cell disorders v0.128 SLC4A1 Danielle Ariti reviewed gene: SLC4A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16227998, 15211439, 10926824, 7949112, 16392641, 8640229, 16227998, 8640229, 16227998; Phenotypes: Cryohydrocytosis MIM# 185020, Distal renal tubular acidosis 4 with haemolytic anaemia MIM# 611590, Ovalocytosis, SA type MIM# 166900, Spherocytosis, type 4 MIM# 612653; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Red cell disorders v0.128 RPL26 Zornitza Stark Marked gene: RPL26 as ready
Red cell disorders v0.128 RPL26 Zornitza Stark Gene: rpl26 has been classified as Red List (Low Evidence).
Red cell disorders v0.128 RPL26 Zornitza Stark Phenotypes for gene: RPL26 were changed from Diamond-Blackfan anemia 11, MIM# 614900 to Diamond-Blackfan anaemia 11, MIM# 614900
Red cell disorders v0.127 RPL26 Zornitza Stark Phenotypes for gene: RPL26 were changed from ?Diamond-Blackfan anemia 11, 614900; 614900 ?Diamond-Blackfan anemia 11 to Diamond-Blackfan anemia 11, MIM# 614900
Red cell disorders v0.126 RPL26 Zornitza Stark Classified gene: RPL26 as Red List (low evidence)
Red cell disorders v0.126 RPL26 Zornitza Stark Gene: rpl26 has been classified as Red List (Low Evidence).
Red cell disorders v0.125 RPL15 Zornitza Stark Marked gene: RPL15 as ready
Red cell disorders v0.125 RPL15 Zornitza Stark Gene: rpl15 has been classified as Green List (High Evidence).
Red cell disorders v0.125 RPL15 Zornitza Stark Phenotypes for gene: RPL15 were changed from Diamond-Blackfan anemia 12, MIM# 615550 to Diamond-Blackfan anaemia 12, MIM# 615550
Red cell disorders v0.124 RPL15 Zornitza Stark Phenotypes for gene: RPL15 were changed from 615550 ?Diamond-Blackfan anaemia 12; ?Diamond-Blackfan anemia 12, 615550; 615550 ?Diamond-Blackfan anemia 1 to Diamond-Blackfan anemia 12, MIM# 615550
Red cell disorders v0.123 RPL15 Zornitza Stark Publications for gene: RPL15 were set to 23812780
Red cell disorders v0.122 RPL15 Zornitza Stark Mode of inheritance for gene: RPL15 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Red cell disorders v0.121 RPL11 Zornitza Stark Marked gene: RPL11 as ready
Red cell disorders v0.121 RPL11 Zornitza Stark Gene: rpl11 has been classified as Green List (High Evidence).
Red cell disorders v0.121 RPL11 Zornitza Stark Phenotypes for gene: RPL11 were changed from Diamond_Blackfan Anemia 7; Inherited Bone Marrow Failure Syndromes; Diamond Blackfan anemia; Diamond-Blackfan Anemia; 612562 Diamond-Blackfan anemia 7; Diamond-Blackfan Anemia 7; 612562 Diamond_Blackfan Anemia 7; DIAMOND-BLACKFAN ANEMIA 7; Diamond-Blackfan anemia 7, 612562 to Diamond-Blackfan anemia 7, MIM# 612562; MONDO:0012938
Red cell disorders v0.120 PKLR Zornitza Stark Marked gene: PKLR as ready
Red cell disorders v0.120 PKLR Zornitza Stark Gene: pklr has been classified as Green List (High Evidence).
Red cell disorders v0.120 PKLR Zornitza Stark Phenotypes for gene: PKLR were changed from 266200 PYRUVATE KINASE DEFICIENCY; Enzyme Disorder; PYRUVATE KINASE DEFICIENCY; 266200 Pyruvate kinase deficiency; Pyruvate kinase deficiency, 266200; Pyruvate kinase deficiency to Adenosine triphosphate, elevated, of erythrocytes, MIM# 102900; Pyruvate kinase deficiency, MIM# 266200
Red cell disorders v0.119 PKLR Zornitza Stark Mode of inheritance for gene: PKLR was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Red cell disorders v0.118 PKLR Zornitza Stark reviewed gene: PKLR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Adenosine triphosphate, elevated, of erythrocytes, MIM# 102900, Pyruvate kinase deficiency, MIM# 266200; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Red cell disorders v0.118 PIEZO1 Zornitza Stark Marked gene: PIEZO1 as ready
Red cell disorders v0.118 PIEZO1 Zornitza Stark Gene: piezo1 has been classified as Green List (High Evidence).
Red cell disorders v0.118 PIEZO1 Zornitza Stark Phenotypes for gene: PIEZO1 were changed from Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, 194380; 194380 Stomatocytosis; Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema; Stomatocytosis; Dehydrated hereditary stomatocytosis; 616843 Lymphatic malformation 6; 194380 Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema; Hereditary xerocytosis to Dehydrated hereditary stomatocytosis with or without pseudohyperkalaemia and/or perinatal oedema, MIM# 194380
Red cell disorders v0.117 PIEZO1 Zornitza Stark Publications for gene: PIEZO1 were set to 22529292; 23695678
Red cell disorders v0.116 PIEZO1 Zornitza Stark Mode of inheritance for gene: PIEZO1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Red cell disorders v0.115 PIEZO1 Zornitza Stark reviewed gene: PIEZO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21944700, 23695678, 23479567; Phenotypes: Dehydrated hereditary stomatocytosis with or without pseudohyperkalaemia and/or perinatal oedema, MIM# 194380; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Red cell disorders v0.115 PFKM Zornitza Stark Marked gene: PFKM as ready
Red cell disorders v0.115 PFKM Zornitza Stark Gene: pfkm has been classified as Green List (High Evidence).
Red cell disorders v0.115 PFKM Zornitza Stark Phenotypes for gene: PFKM were changed from Glycogen storage disease VII, 232800; 232800 Glycogen storage disease VII to Glycogen storage disease VII, MIM# 232800
Red cell disorders v0.114 PFKM Zornitza Stark Publications for gene: PFKM were set to 7513946; 2140573
Red cell disorders v0.113 PFKM Zornitza Stark reviewed gene: PFKM: Rating: GREEN; Mode of pathogenicity: None; Publications: 24427140, 27066546, 30792690; Phenotypes: Glycogen storage disease VII, MIM# 232800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9144 NT5C3A Zornitza Stark Marked gene: NT5C3A as ready
Mendeliome v0.9144 NT5C3A Zornitza Stark Gene: nt5c3a has been classified as Green List (High Evidence).
Mendeliome v0.9144 NT5C3A Zornitza Stark Phenotypes for gene: NT5C3A were changed from to Anaemia, haemolytic, due to UMPH1 deficiency, MIM# 266120
Mendeliome v0.9143 NT5C3A Zornitza Stark Publications for gene: NT5C3A were set to
Mendeliome v0.9142 NT5C3A Zornitza Stark Mode of inheritance for gene: NT5C3A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9141 NT5C3A Zornitza Stark reviewed gene: NT5C3A: Rating: GREEN; Mode of pathogenicity: None; Publications: 11369620, 12714505, 30951028, 25153905; Phenotypes: Anaemia, haemolytic, due to UMPH1 deficiency, MIM# 266120; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Red cell disorders v0.113 NT5C3A Zornitza Stark Marked gene: NT5C3A as ready
Red cell disorders v0.113 NT5C3A Zornitza Stark Gene: nt5c3a has been classified as Green List (High Evidence).
Red cell disorders v0.113 NT5C3A Zornitza Stark Phenotypes for gene: NT5C3A were changed from Anemia, hemolytic, due to UMPH1 deficiency, 266120; 266120 Anemia, hemolytic, due to UMPH1 deficiency to Anaemia, haemolytic, due to UMPH1 deficiency, MIM# 266120
Red cell disorders v0.112 NT5C3A Zornitza Stark Publications for gene: NT5C3A were set to 11369620; 12714505
Red cell disorders v0.111 NT5C3A Zornitza Stark reviewed gene: NT5C3A: Rating: GREEN; Mode of pathogenicity: None; Publications: 11369620, 12714505, 30951028, 25153905; Phenotypes: Anaemia, haemolytic, due to UMPH1 deficiency, MIM# 266120; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Oligodontia v0.6 WNT10B Zornitza Stark Marked gene: WNT10B as ready
Oligodontia v0.6 WNT10B Zornitza Stark Gene: wnt10b has been classified as Green List (High Evidence).
Oligodontia v0.6 WNT10B Zornitza Stark Classified gene: WNT10B as Green List (high evidence)
Oligodontia v0.6 WNT10B Zornitza Stark Gene: wnt10b has been classified as Green List (High Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.51 RHOBTB2 Zornitza Stark Marked gene: RHOBTB2 as ready
Alternating Hemiplegia and Hemiplegic Migraine v0.51 RHOBTB2 Zornitza Stark Gene: rhobtb2 has been classified as Green List (High Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.51 RHOBTB2 Zornitza Stark Classified gene: RHOBTB2 as Green List (high evidence)
Alternating Hemiplegia and Hemiplegic Migraine v0.51 RHOBTB2 Zornitza Stark Gene: rhobtb2 has been classified as Green List (High Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.50 RHOBTB2 Zornitza Stark gene: RHOBTB2 was added
gene: RHOBTB2 was added to Alternating Hemiplegia and Hemiplegic Migraine. Sources: Literature
Mode of inheritance for gene: RHOBTB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RHOBTB2 were set to 33504645
Phenotypes for gene: RHOBTB2 were set to Developmental and epileptic encephalopathy 64 618004; Alternating hemiplegia
Review for gene: RHOBTB2 was set to GREEN
Added comment: Eleven affected patients were identified. All had heterozygous missense variants involving exon 9 of RHOBTB2, confirmed as de novo in 9 cases. All had a complex motor phenotype, including at least 2 different kinds of movement disorder, e.g., ataxia and dystonia. Many patients demonstrated several features fulfilling the criteria for AHC: 10 patients had a movement disorder including paroxysmal elements, and 8 experienced hemiplegic episodes. In contrast to classic AHC, commonly caused by mutations in ATP1A3, these events were reported later only in RHOBTB2 mutation-positive patients from 20 months of age.

All had ID, and many had seizures, so this represents an expansion of the phenotype rather than a distinct disorder.
Sources: Literature
Microcephaly v1.46 COPB2 Zornitza Stark Classified gene: COPB2 as Amber List (moderate evidence)
Microcephaly v1.46 COPB2 Zornitza Stark Gene: copb2 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.45 COPB2 Zornitza Stark edited their review of gene: COPB2: Added comment: Loss-of-function variants in COPB2, a component of the COPI coatomer complex, in six individuals from five unrelated families. 4 are heterozygous and one family with two sibs with homozygous variant, previously reported.
All presenting with a clinical spectrum of osteoporosis or osteopaenia, many with recurrent fractures, and developmental delay of variable severity. Functional data.

Note one of the individuals with heterozygous variant had significant microcephaly in addition to the two sibs with bi-allelic variants.; Changed rating: AMBER; Changed publications: 29036432, 34450031; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v0.65 COPB2 Zornitza Stark Marked gene: COPB2 as ready
Osteogenesis Imperfecta and Osteoporosis v0.65 COPB2 Zornitza Stark Gene: copb2 has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.65 COPB2 Zornitza Stark Classified gene: COPB2 as Green List (high evidence)
Osteogenesis Imperfecta and Osteoporosis v0.65 COPB2 Zornitza Stark Gene: copb2 has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.64 COPB2 Zornitza Stark gene: COPB2 was added
gene: COPB2 was added to Osteogenesis Imperfecta. Sources: Literature
Mode of inheritance for gene: COPB2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: COPB2 were set to 34450031
Phenotypes for gene: COPB2 were set to Osteoporosis, recurrent fractures and developmental delay
Review for gene: COPB2 was set to GREEN
Added comment: Loss-of-function variants in COPB2, a component of the COPI coatomer complex, in six individuals from five unrelated families. 4 are heterozygous and one family with two sibs with homozygous variant, previously reported.
All presenting with a clinical spectrum of osteoporosis or osteopaenia, many with recurrent fractures, and developmental delay of variable severity. Functional data.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4116 COPB2 Zornitza Stark Classified gene: COPB2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4116 COPB2 Zornitza Stark Gene: copb2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4115 COPB2 Zornitza Stark reviewed gene: COPB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Oligodontia v0.5 WNT10B Ain Roesley gene: WNT10B was added
gene: WNT10B was added to Oligodontia. Sources: Literature
Mode of inheritance for gene: WNT10B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: WNT10B were set to 27321946; 29364501; 21554266; 31050392
Phenotypes for gene: WNT10B were set to Tooth agenesis, selective, 8 MIM#617073
Penetrance for gene: WNT10B were set to unknown
Review for gene: WNT10B was set to GREEN
Added comment: PMID: 27321946; 4 unrelated families (including 1 with 3 affecteds). 3x missense and 1x truncating. Luciferase assays demonstrated LoF compared to WT.


PMID: 29364501; 7 unrelated families all missense. Arg159Pro identified in 4 families and family#5 also had variants in WNT10A.
Re-evaluation of a previously reported family #8 - 1 heterozygote who only had tooth agenesis while 6 other relatives who were homozygotes also had split hand-foot malformation

NOTE: No genotype phenotype correlation between AD tooth agenesis and AR split hand-foot malformation - missense have also been reported in SHFM (PMID: 31050392). While it's noted that most reports of SHFM did not investigate oligodontia in their patients or carrier parents, PMID: 21554266 noted their carrier parents were healthy and clinically distinguishable
Sources: Literature
Congenital Disorders of Glycosylation v1.18 SLC37A4 Zornitza Stark Phenotypes for gene: SLC37A4 were changed from Congenital disorder of glycosylation type II to Congenital disorder of glycosylation, type IIw, MIM# 619525
Congenital Disorders of Glycosylation v1.17 SLC37A4 Zornitza Stark edited their review of gene: SLC37A4: Changed phenotypes: Congenital disorder of glycosylation, type IIw 619525
Mendeliome v0.9141 IMPG1 Zornitza Stark Phenotypes for gene: IMPG1 were changed from Macular dystrophy, vitelliform, 4, OMIM:616151; Retinitis pigmentosa, MONDO:0019200 to Macular dystrophy, vitelliform, 4, OMIM:616151; Retinitis pigmentosa, MONDO:0019200; Retinitis pigmentosa 91, MIM# 153870
Mendeliome v0.9140 IMPG1 Zornitza Stark reviewed gene: IMPG1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinitis pigmentosa 91, MIM# 153870; Mode of inheritance: None
Retinitis pigmentosa v0.100 IMPG1 Zornitza Stark Phenotypes for gene: IMPG1 were changed from Retinitis pigmentosa, MONDO:0019200 to Retinitis pigmentosa, MONDO:0019200; Retinitis pigmentosa 91, MIM# 153870
Retinitis pigmentosa v0.99 IMPG1 Zornitza Stark edited their review of gene: IMPG1: Changed phenotypes: Retinitis pigmentosa, MONDO:0019200, Retinitis pigmentosa 91, MIM# 153870
Mendeliome v0.9140 ABCC11 Zornitza Stark Marked gene: ABCC11 as ready
Mendeliome v0.9140 ABCC11 Zornitza Stark Gene: abcc11 has been classified as Red List (Low Evidence).
Mendeliome v0.9140 ABCC11 Zornitza Stark Phenotypes for gene: ABCC11 were changed from to [Axillary odor, variation in] 117800; [Colostrum secretion, variation in] 117800; [Earwax, wet/dry] 117800
Mendeliome v0.9139 ABCC11 Zornitza Stark Classified gene: ABCC11 as Red List (low evidence)
Mendeliome v0.9139 ABCC11 Zornitza Stark Gene: abcc11 has been classified as Red List (Low Evidence).
Mendeliome v0.9138 ABCC11 Zornitza Stark reviewed gene: ABCC11: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: [Axillary odor, variation in] 117800, [Colostrum secretion, variation in] 117800, [Earwax, wet/dry] 117800; Mode of inheritance: None
Red cell disorders v0.111 PUS1 Zornitza Stark Marked gene: PUS1 as ready
Red cell disorders v0.111 PUS1 Zornitza Stark Gene: pus1 has been classified as Green List (High Evidence).
Red cell disorders v0.111 PUS1 Zornitza Stark Phenotypes for gene: PUS1 were changed from 600462 Myopathy, lactic acidosis, and sideroblastic anemia 1; Myopathy, Lactic Acidosis, and Sideroblastic Anemia, 600462; 600462 Myopathy, Lactic Acidosis, and Sideroblastic Anemia to Myopathy, lactic acidosis, and sideroblastic anaemia 1, MIM# 600462
Red cell disorders v0.110 PUS1 Zornitza Stark Publications for gene: PUS1 were set to 15108122; 15772074
Red cell disorders v0.109 PUS1 Zornitza Stark edited their review of gene: PUS1: Changed phenotypes: Myopathy, lactic acidosis, and sideroblastic anaemia 1, MIM# 600462
Red cell disorders v0.109 HSPA9 Zornitza Stark Marked gene: HSPA9 as ready
Red cell disorders v0.109 HSPA9 Zornitza Stark Gene: hspa9 has been classified as Green List (High Evidence).
Red cell disorders v0.109 HSPA9 Zornitza Stark Phenotypes for gene: HSPA9 were changed from sideroblastic anaemia; 182170 Sideroblastic anaemia 4; 182170 sideroblastic anaemia type 4; Sideroblastic anaemia type 4, 182170 to Anaemia, sideroblastic, 4, MIM# 182170
Red cell disorders v0.108 HSPA9 Zornitza Stark reviewed gene: HSPA9: Rating: GREEN; Mode of pathogenicity: None; Publications: 26491070; Phenotypes: Anaemia, sideroblastic, 4, MIM# 182170; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9138 KCNN4 Zornitza Stark Publications for gene: KCNN4 were set to 26148990; 26198474; 26178367
Mendeliome v0.9137 KCNN4 Zornitza Stark changed review comment from: At least three families reported.
Sources: Expert list; to: Well established gene-disease association, more than 10 families and functional data.
Mendeliome v0.9137 KCNN4 Zornitza Stark edited their review of gene: KCNN4: Changed publications: 26148990, 26198474, 26178367, 33519508, 31091145, 28619848; Changed phenotypes: Dehydrated hereditary stomatocytosis 2, MIM# 616689
Red cell disorders v0.108 KCNN4 Zornitza Stark Marked gene: KCNN4 as ready
Red cell disorders v0.108 KCNN4 Zornitza Stark Gene: kcnn4 has been classified as Green List (High Evidence).
Red cell disorders v0.108 KCNN4 Zornitza Stark Phenotypes for gene: KCNN4 were changed from Hereditary Xerocytosis; 616689 Dehydrated hereditary stomatocytosis 2 to Dehydrated hereditary stomatocytosis 2, MIM# 616689
Red cell disorders v0.107 KCNN4 Zornitza Stark Publications for gene: KCNN4 were set to 26148990; 26178367
Red cell disorders v0.106 KCNN4 Zornitza Stark Mode of inheritance for gene: KCNN4 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Red cell disorders v0.105 KCNN4 Zornitza Stark reviewed gene: KCNN4: Rating: GREEN; Mode of pathogenicity: None; Publications: 26148990, 26198474, 26178367, 33519508, 31091145, 28619848; Phenotypes: Dehydrated hereditary stomatocytosis 2, MIM# 616689; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Red cell disorders v0.105 KLF1 Zornitza Stark Marked gene: KLF1 as ready
Red cell disorders v0.105 KLF1 Zornitza Stark Gene: klf1 has been classified as Green List (High Evidence).
Red cell disorders v0.105 KLF1 Zornitza Stark Phenotypes for gene: KLF1 were changed from 613673 Congenital dyserythropoietic anaemia type 4; Congenital Dyserythropoietic Anemia; 613673 Congenital Dyserythropoietic Anemia; Dyserythropoietic anemia, congenital, type IV, 613673; Dyserythropoietic anemia, congenital, type IV to Dyserythropoietic anaemia, congenital, type IV, MIM# 613673; MONDO:0013355
Red cell disorders v0.104 KLF1 Zornitza Stark Publications for gene: KLF1 were set to 21055716; 29200155
Red cell disorders v0.103 HK1 Zornitza Stark Marked gene: HK1 as ready
Red cell disorders v0.103 HK1 Zornitza Stark Gene: hk1 has been classified as Green List (High Evidence).
Red cell disorders v0.103 HK1 Zornitza Stark Phenotypes for gene: HK1 were changed from 235700 Enzyme Disorder; Hemolytic anemia due to hexokinase deficiency, 235700; 235700 Hemolytic anemia due to hexokinase deficiency; Hemolytic anemia due to hexokinase deficiency; Enzyme Disorder to Haemolytic anaemia due to hexokinase deficiency, MIM# 235700
Red cell disorders v0.102 HK1 Zornitza Stark Publications for gene: HK1 were set to 7655856; 12393545
Red cell disorders v0.101 HK1 Zornitza Stark reviewed gene: HK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 7655856, 12393545, 33361148, 31119733, 27282571; Phenotypes: Haemolytic anaemia due to hexokinase deficiency, MIM# 235700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1193 HCN4 Zornitza Stark Marked gene: HCN4 as ready
Genetic Epilepsy v0.1193 HCN4 Zornitza Stark Gene: hcn4 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1193 HCN4 Zornitza Stark gene: HCN4 was added
gene: HCN4 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: HCN4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HCN4 were set to 30127718; 29588962
Phenotypes for gene: HCN4 were set to {Epilepsy, idiopathic generalized, susceptibility to, 18}, MIM# 619521
Review for gene: HCN4 was set to RED
Added comment: Two families reported. Variant did not segregate with disease in one (PMID 29588962), and was present in two affected sibs from another family reported in PMID 30127718, some functional data to support impact of variant on protein function.
Sources: Expert list
Red cell disorders v0.101 KIF23 Zornitza Stark Marked gene: KIF23 as ready
Red cell disorders v0.101 KIF23 Zornitza Stark Gene: kif23 has been classified as Red List (Low Evidence).
Red cell disorders v0.101 KIF23 Zornitza Stark Phenotypes for gene: KIF23 were changed from Enzyme Disorder; Anaemia, dyserythropoietic congenital, type III; Congenital dyserythropoietic anemia (CDA); Congenital dyserythropoietic anemia type III; 605064 Congenital dyserythropoietic anaemia type 3; CDA III to Congenital dyserythropoietic anemia type III
Red cell disorders v0.100 KIF23 Zornitza Stark Classified gene: KIF23 as Red List (low evidence)
Red cell disorders v0.100 KIF23 Zornitza Stark Gene: kif23 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.4115 MTRR Zornitza Stark Marked gene: MTRR as ready
Intellectual disability syndromic and non-syndromic v0.4115 MTRR Zornitza Stark Gene: mtrr has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4115 MTRR Zornitza Stark Phenotypes for gene: MTRR were changed from to Homocystinuria-megaloblastic anaemia, cbl E type, MIM# 236270
Intellectual disability syndromic and non-syndromic v0.4114 MTRR Zornitza Stark Publications for gene: MTRR were set to
Intellectual disability syndromic and non-syndromic v0.4113 MTRR Zornitza Stark Mode of inheritance for gene: MTRR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4112 MTRR Zornitza Stark reviewed gene: MTRR: Rating: GREEN; Mode of pathogenicity: None; Publications: 12555939, 15714522; Phenotypes: Homocystinuria-megaloblastic anaemia, cbl E type, MIM# 236270; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9137 MTRR Zornitza Stark Marked gene: MTRR as ready
Mendeliome v0.9137 MTRR Zornitza Stark Gene: mtrr has been classified as Green List (High Evidence).
Mendeliome v0.9137 MTRR Zornitza Stark Phenotypes for gene: MTRR were changed from to Homocystinuria-megaloblastic anaemia, cbl E type, MIM# 236270
Mendeliome v0.9136 MTRR Zornitza Stark Publications for gene: MTRR were set to
Mendeliome v0.9135 MTRR Zornitza Stark Mode of inheritance for gene: MTRR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9134 MTRR Zornitza Stark reviewed gene: MTRR: Rating: GREEN; Mode of pathogenicity: None; Publications: 12555939, 15714522; Phenotypes: Homocystinuria-megaloblastic anaemia, cbl E type, MIM# 236270; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Red cell disorders v0.99 MTRR Zornitza Stark Marked gene: MTRR as ready
Red cell disorders v0.99 MTRR Zornitza Stark Gene: mtrr has been classified as Green List (High Evidence).
Red cell disorders v0.99 MTRR Zornitza Stark Phenotypes for gene: MTRR were changed from Homocystinuria-megaloblastic anemia, cbl E type, 236270; 236270 Homocystinuria-megaloblastic anemia, cbl E type to Homocystinuria-megaloblastic anaemia, cbl E type, MIM# 236270
Red cell disorders v0.98 MTRR Zornitza Stark reviewed gene: MTRR: Rating: GREEN; Mode of pathogenicity: None; Publications: 12555939, 15714522; Phenotypes: Homocystinuria-megaloblastic anaemia, cbl E type, MIM# 236270; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4112 MTR Zornitza Stark Marked gene: MTR as ready
Intellectual disability syndromic and non-syndromic v0.4112 MTR Zornitza Stark Gene: mtr has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4112 MTR Zornitza Stark Phenotypes for gene: MTR were changed from to Homocystinuria-megaloblastic anaemia, cblG complementation type, MIM# 250940
Intellectual disability syndromic and non-syndromic v0.4111 MTR Zornitza Stark Publications for gene: MTR were set to
Intellectual disability syndromic and non-syndromic v0.4110 MTR Zornitza Stark Mode of inheritance for gene: MTR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4109 MTR Zornitza Stark reviewed gene: MTR: Rating: GREEN; Mode of pathogenicity: None; Publications: 8968736, 8968737, 9683607, 12068375; Phenotypes: Homocystinuria-megaloblastic anaemia, cblG complementation type, MIM# 250940; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9134 MTR Zornitza Stark Marked gene: MTR as ready
Mendeliome v0.9134 MTR Zornitza Stark Gene: mtr has been classified as Green List (High Evidence).
Mendeliome v0.9134 MTR Zornitza Stark Phenotypes for gene: MTR were changed from to Homocystinuria-megaloblastic anaemia, cblG complementation type, MIM# 250940
Mendeliome v0.9133 MTR Zornitza Stark Publications for gene: MTR were set to
Mendeliome v0.9132 MTR Zornitza Stark Mode of inheritance for gene: MTR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9131 MTR Zornitza Stark reviewed gene: MTR: Rating: GREEN; Mode of pathogenicity: None; Publications: 8968736, 8968737, 9683607, 12068375; Phenotypes: Homocystinuria-megaloblastic anaemia, cblG complementation type, MIM# 250940; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Red cell disorders v0.98 MTR Zornitza Stark Marked gene: MTR as ready
Red cell disorders v0.98 MTR Zornitza Stark Gene: mtr has been classified as Green List (High Evidence).
Red cell disorders v0.98 MTR Zornitza Stark Phenotypes for gene: MTR were changed from Homocystinuria-megaloblastic anemia, cblG complementation type, 250940; 250940 Homocystinuria-megaloblastic anemia, cblG complementation type to Homocystinuria-megaloblastic anaemia, cblG complementation type, MIM# 250940
Red cell disorders v0.97 MTR Zornitza Stark Publications for gene: MTR were set to 9683607; 12068375
Red cell disorders v0.96 MTR Zornitza Stark reviewed gene: MTR: Rating: GREEN; Mode of pathogenicity: None; Publications: 8968736, 8968737, 9683607, 12068375; Phenotypes: Homocystinuria-megaloblastic anaemia, cblG complementation type, MIM# 250940; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Autoinflammatory Disorders v0.121 LPIN2 Zornitza Stark Marked gene: LPIN2 as ready
Autoinflammatory Disorders v0.121 LPIN2 Zornitza Stark Gene: lpin2 has been classified as Green List (High Evidence).
Autoinflammatory Disorders v0.121 LPIN2 Zornitza Stark Phenotypes for gene: LPIN2 were changed from to Majeed syndrome, MIM# 609628; Chronic recurrent multifocal osteomyelitis with congenital dyserythropoietic anaemia
Autoinflammatory Disorders v0.120 LPIN2 Zornitza Stark Publications for gene: LPIN2 were set to
Autoinflammatory Disorders v0.119 LPIN2 Zornitza Stark Mode of inheritance for gene: LPIN2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Autoinflammatory Disorders v0.118 LPIN2 Zornitza Stark reviewed gene: LPIN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 15994876, 33993107, 33670882, 33314777, 31727123; Phenotypes: Majeed syndrome, MIM# 609628, Chronic recurrent multifocal osteomyelitis with congenital dyserythropoietic anaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9131 LPIN2 Zornitza Stark Marked gene: LPIN2 as ready