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Mendeliome v0.11448 NCF2 Zornitza Stark Gene: ncf2 has been classified as Green List (High Evidence).
Mendeliome v0.11448 NCF2 Zornitza Stark Phenotypes for gene: NCF2 were changed from to Chronic granulomatous disease 2, autosomal recessive, MIM# 233710
Mendeliome v0.11447 NCF2 Zornitza Stark Publications for gene: NCF2 were set to
Mendeliome v0.11446 NCF2 Zornitza Stark Mode of inheritance for gene: NCF2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Amelogenesis imperfecta v1.3 DSPP Zornitza Stark Marked gene: DSPP as ready
Amelogenesis imperfecta v1.3 DSPP Zornitza Stark Gene: dspp has been classified as Green List (High Evidence).
Mendeliome v0.11445 SALL4 Zornitza Stark Marked gene: SALL4 as ready
Mendeliome v0.11445 SALL4 Zornitza Stark Gene: sall4 has been classified as Green List (High Evidence).
Mendeliome v0.11445 SALL4 Zornitza Stark Phenotypes for gene: SALL4 were changed from to Duane-radial ray syndrome, MIM# 607323; MONDO:0011812; IVIC syndrome, MIM# 147750; MONDO:0007836
Mendeliome v0.11444 SALL4 Zornitza Stark Publications for gene: SALL4 were set to
Mendeliome v0.11443 SALL4 Zornitza Stark Mode of inheritance for gene: SALL4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11442 SALL4 Zornitza Stark reviewed gene: SALL4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Duane-radial ray syndrome, MIM# 607323, MONDO:0011812, IVIC syndrome, MIM# 147750, MONDO:0007836; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11442 TYROBP Zornitza Stark Marked gene: TYROBP as ready
Mendeliome v0.11442 TYROBP Zornitza Stark Gene: tyrobp has been classified as Green List (High Evidence).
Mendeliome v0.11442 TYROBP Zornitza Stark Phenotypes for gene: TYROBP were changed from to Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1, MIM# 221770
Mendeliome v0.11441 TYROBP Zornitza Stark Publications for gene: TYROBP were set to
Mendeliome v0.11440 TYROBP Zornitza Stark Mode of inheritance for gene: TYROBP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11439 TYROBP Zornitza Stark reviewed gene: TYROBP: Rating: GREEN; Mode of pathogenicity: None; Publications: 10888890, 12370476, 27904822; Phenotypes: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1, MIM# 221770; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Defects of intrinsic and innate immunity v0.94 IRAK4 Zornitza Stark Marked gene: IRAK4 as ready
Defects of intrinsic and innate immunity v0.94 IRAK4 Zornitza Stark Gene: irak4 has been classified as Green List (High Evidence).
Defects of intrinsic and innate immunity v0.94 IRAK4 Zornitza Stark Phenotypes for gene: IRAK4 were changed from to Immunodeficiency 67, MIM# 607676
Defects of intrinsic and innate immunity v0.93 IRAK4 Zornitza Stark Publications for gene: IRAK4 were set to
Defects of intrinsic and innate immunity v0.92 IRAK4 Zornitza Stark Mode of inheritance for gene: IRAK4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Defects of intrinsic and innate immunity v0.91 IRAK4 Zornitza Stark reviewed gene: IRAK4: Rating: GREEN; Mode of pathogenicity: None; Publications: 26825884, 17878374, 17544092, 16950813; Phenotypes: Immunodeficiency 67, MIM# 607676; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11439 IRAK4 Zornitza Stark Marked gene: IRAK4 as ready
Mendeliome v0.11439 IRAK4 Zornitza Stark Gene: irak4 has been classified as Green List (High Evidence).
Mendeliome v0.11439 IRAK4 Zornitza Stark Phenotypes for gene: IRAK4 were changed from to Immunodeficiency 67, MIM# 607676
Mendeliome v0.11438 IRAK4 Zornitza Stark Publications for gene: IRAK4 were set to
Mendeliome v0.11437 IRAK4 Zornitza Stark Mode of inheritance for gene: IRAK4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11436 IRAK4 Zornitza Stark reviewed gene: IRAK4: Rating: GREEN; Mode of pathogenicity: None; Publications: 26825884, 17878374, 17544092, 16950813; Phenotypes: Immunodeficiency 67, MIM# 607676; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11436 TYK2 Manny Jacobs reviewed gene: TYK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 17088085, 17521577, 26304966; Phenotypes: # 611521 IMMUNODEFICIENCY 35; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11436 INSR Zornitza Stark Marked gene: INSR as ready
Mendeliome v0.11436 INSR Zornitza Stark Gene: insr has been classified as Green List (High Evidence).
Mendeliome v0.11436 INSR Zornitza Stark Phenotypes for gene: INSR were changed from to Hyperinsulinemic hypoglycemia, familial, 5, MIM# 609968; Leprechaunism, MIM# 246200; Rabson-Mendenhall syndrome, MIM# 262190
Mendeliome v0.11435 INSR Zornitza Stark Publications for gene: INSR were set to
Mendeliome v0.11434 INSR Zornitza Stark Mode of inheritance for gene: INSR was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11433 INSR Zornitza Stark reviewed gene: INSR: Rating: GREEN; Mode of pathogenicity: None; Publications: 34965699; Phenotypes: Hyperinsulinemic hypoglycemia, familial, 5, MIM# 609968, Leprechaunism, MIM# 246200, Rabson-Mendenhall syndrome, MIM# 262190; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11433 INS Zornitza Stark Marked gene: INS as ready
Mendeliome v0.11433 INS Zornitza Stark Gene: ins has been classified as Green List (High Evidence).
Mendeliome v0.11433 INS Zornitza Stark Phenotypes for gene: INS were changed from to Diabetes mellitus, insulin-dependent, 2, MIM# 125852; Diabetes mellitus, permanent neonatal 4, MIM# 618858; Maturity-onset diabetes of the young, type 10, MIM# 613370
Mendeliome v0.11432 INS Zornitza Stark Publications for gene: INS were set to
Mendeliome v0.11431 INS Zornitza Stark Mode of inheritance for gene: INS was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11430 INS Zornitza Stark reviewed gene: INS: Rating: GREEN; Mode of pathogenicity: None; Publications: 18162506; Phenotypes: Diabetes mellitus, insulin-dependent, 2, MIM# 125852, Diabetes mellitus, permanent neonatal 4, MIM# 618858, Maturity-onset diabetes of the young, type 10, MIM# 613370; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Predominantly Antibody Deficiency v0.102 INO80 Zornitza Stark Marked gene: INO80 as ready
Predominantly Antibody Deficiency v0.102 INO80 Zornitza Stark Gene: ino80 has been classified as Amber List (Moderate Evidence).
Predominantly Antibody Deficiency v0.102 INO80 Zornitza Stark Phenotypes for gene: INO80 were changed from to Primary immunodeficiency, MONDO:0003778
Predominantly Antibody Deficiency v0.101 INO80 Zornitza Stark Publications for gene: INO80 were set to
Predominantly Antibody Deficiency v0.100 INO80 Zornitza Stark Mode of inheritance for gene: INO80 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Predominantly Antibody Deficiency v0.99 INO80 Zornitza Stark Classified gene: INO80 as Amber List (moderate evidence)
Predominantly Antibody Deficiency v0.99 INO80 Zornitza Stark Gene: ino80 has been classified as Amber List (Moderate Evidence).
Predominantly Antibody Deficiency v0.98 INO80 Zornitza Stark reviewed gene: INO80: Rating: AMBER; Mode of pathogenicity: None; Publications: 25312759; Phenotypes: Primary immunodeficiency, MONDO:0003778; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11430 INO80 Zornitza Stark Marked gene: INO80 as ready
Mendeliome v0.11430 INO80 Zornitza Stark Gene: ino80 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11430 INO80 Zornitza Stark Phenotypes for gene: INO80 were changed from to Primary immunodeficiency, MONDO:0003778
Mendeliome v0.11429 INO80 Zornitza Stark Publications for gene: INO80 were set to
Mendeliome v0.11428 INO80 Zornitza Stark Mode of inheritance for gene: INO80 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11427 INO80 Zornitza Stark Classified gene: INO80 as Amber List (moderate evidence)
Mendeliome v0.11427 INO80 Zornitza Stark Gene: ino80 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11426 TYMP Manny Jacobs reviewed gene: TYMP: Rating: GREEN; Mode of pathogenicity: None; Publications: 21933806; Phenotypes: # 603041 MITOCHONDRIAL DNA DEPLETION SYNDROME 1 (MNGIE TYPE); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11426 INO80 Zornitza Stark reviewed gene: INO80: Rating: AMBER; Mode of pathogenicity: None; Publications: 25312759; Phenotypes: Primary immunodeficiency, MONDO:0003778; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11426 IMPAD1 Zornitza Stark Marked gene: IMPAD1 as ready
Mendeliome v0.11426 IMPAD1 Zornitza Stark Gene: impad1 has been classified as Green List (High Evidence).
Mendeliome v0.11426 IMPAD1 Zornitza Stark Phenotypes for gene: IMPAD1 were changed from to Chondrodysplasia with joint dislocations, GPAPP type MIM#614078
Mendeliome v0.11425 IMPAD1 Zornitza Stark Publications for gene: IMPAD1 were set to
Mendeliome v0.11424 IMPAD1 Zornitza Stark Mode of inheritance for gene: IMPAD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11423 IMPAD1 Zornitza Stark Deleted their review
Mendeliome v0.11423 IMPAD1 Zornitza Stark reviewed gene: IMPAD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22887726, 21549340; Phenotypes: Chondrodysplasia with joint dislocations, GPAPP type MIM#614078; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11423 ILF2 Zornitza Stark changed review comment from: Cannot find evidence for association with Mendelian disease.; to: Limited data to support association with autism: two variants in a large ASD cohort and other supportive evidence. Assessed as 'strong candidate' by SFARI.
Autism v0.174 ILF2 Zornitza Stark Marked gene: ILF2 as ready
Autism v0.174 ILF2 Zornitza Stark Gene: ilf2 has been classified as Red List (Low Evidence).
Autism v0.174 ILF2 Zornitza Stark Phenotypes for gene: ILF2 were changed from to Autism
Autism v0.173 ILF2 Zornitza Stark Publications for gene: ILF2 were set to
Mendeliome v0.11423 ILF2 Zornitza Stark edited their review of gene: ILF2: Changed publications: 26402605; Changed phenotypes: Autism
Autism v0.172 ILF2 Zornitza Stark Classified gene: ILF2 as Red List (low evidence)
Autism v0.172 ILF2 Zornitza Stark Gene: ilf2 has been classified as Red List (Low Evidence).
Autism v0.171 ILF2 Zornitza Stark Classified gene: ILF2 as Red List (low evidence)
Autism v0.171 ILF2 Zornitza Stark Gene: ilf2 has been classified as Red List (Low Evidence).
Autism v0.170 ILF2 Zornitza Stark reviewed gene: ILF2: Rating: RED; Mode of pathogenicity: None; Publications: 26402605; Phenotypes: Autism; Mode of inheritance: None
Mendeliome v0.11423 ILF2 Zornitza Stark Marked gene: ILF2 as ready
Mendeliome v0.11423 ILF2 Zornitza Stark Gene: ilf2 has been classified as Red List (Low Evidence).
Mendeliome v0.11423 TYR Manny Jacobs reviewed gene: TYR: Rating: GREEN; Mode of pathogenicity: None; Publications: 17980020; Phenotypes: Albinism, oculocutaneous, type IA, OMIM 203100, Albinism, oculocutaneous, type IB, OMIM 606952; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11423 SALL4 Samantha Ayres reviewed gene: SALL4: Rating: ; Mode of pathogenicity: None; Publications: 20301547; Phenotypes: Duane-radial ray syndrome, MIM# 607323, MONDO:0011812, IVIC syndrome, MIM# 147750, MONDO:0007836; Mode of inheritance: None
Mendeliome v0.11423 TYROBP Manny Jacobs reviewed gene: TYROBP: Rating: GREEN; Mode of pathogenicity: None; Publications: 27904822; Phenotypes: # 221770 POLYCYSTIC LIPOMEMBRANOUS OSTEODYSPLASIA WITH SCLEROSING LEUKOENCEPHALOPATHY 1; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11423 ILF2 Zornitza Stark Classified gene: ILF2 as Red List (low evidence)
Mendeliome v0.11423 ILF2 Zornitza Stark Gene: ilf2 has been classified as Red List (Low Evidence).
Mendeliome v0.11422 ILF2 Zornitza Stark reviewed gene: ILF2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mitochondrial disease v0.711 NDUFA10 Krithika Murali reviewed gene: NDUFA10: Rating: GREEN; Mode of pathogenicity: None; Publications: 26741492, 21150889; Phenotypes: Mitochondrial complex I deficiency, nuclear type 22 - MIM#618243; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Regression v0.403 NDUFA10 Krithika Murali reviewed gene: NDUFA10: Rating: GREEN; Mode of pathogenicity: None; Publications: 26741492, 21150889; Phenotypes: Mitochondrial complex I deficiency, nuclear type 22 - MIM#618243; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1481 NDUFA10 Krithika Murali reviewed gene: NDUFA10: Rating: GREEN; Mode of pathogenicity: None; Publications: 26741492, 21150889; Phenotypes: Mitochondrial complex I deficiency, nuclear type 22 - MIM#618243; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11422 NDUFA10 Krithika Murali reviewed gene: NDUFA10: Rating: GREEN; Mode of pathogenicity: None; Publications: 26741492, 21150889; Phenotypes: Mitochondrial complex I deficiency, nuclear type 22 - MIM#618243; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11422 NDST1 Krithika Murali reviewed gene: NDST1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25125150, 21937992, 32878022, 28211985; Phenotypes: Mental retardation, autosomal recessive 46 - MIM#616116; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4572 NDST1 Krithika Murali reviewed gene: NDST1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25125150, 21937992, 32878022, 28211985; Phenotypes: Mental retardation, autosomal recessive 46 - MIM#616116; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1481 NDST1 Krithika Murali gene: NDST1 was added
gene: NDST1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: NDST1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDST1 were set to 25125150; 21937992; 32878022; 28211985
Phenotypes for gene: NDST1 were set to Mental retardation, autosomal recessive 46 - MIM#616116
Review for gene: NDST1 was set to GREEN
Added comment: At least 8 unrelated families reported. Biallelic NDST1 variants associated with intellectual disability, muscular hypotonia, epilepsy (feature noted in majority of published individuals, onset in infancy/childhood), and postnatal growth deficiency
Sources: Literature
Mendeliome v0.11422 TYRP1 Manny Jacobs reviewed gene: TYRP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9345097; Phenotypes: Albinism, oculocutaneous, type III, MIM# 203290, MONDO:0008747; Mode of inheritance: None; Current diagnostic: yes
Mendeliome v0.11422 NCR3 Krithika Murali reviewed gene: NCR3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.11422 NCOA4 Krithika Murali reviewed gene: NCOA4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.11422 NCF4 Krithika Murali reviewed gene: NCF4: Rating: GREEN; Mode of pathogenicity: None; Publications: 19692703, 16880254, 29969437; Phenotypes: Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III MIM#613960; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Inflammatory bowel disease v0.67 NCF2 Krithika Murali reviewed gene: NCF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 7795241, 10498624; Phenotypes: Chronic granulomatous disease 2, autosomal recessive, MIM# 233710; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11422 NCF2 Krithika Murali reviewed gene: NCF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 7795241, 10498624; Phenotypes: Chronic granulomatous disease 2, autosomal recessive, MIM# 233710; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Defects of intrinsic and innate immunity v0.91 IFNGR2 Zornitza Stark Marked gene: IFNGR2 as ready
Defects of intrinsic and innate immunity v0.91 IFNGR2 Zornitza Stark Gene: ifngr2 has been classified as Green List (High Evidence).
Defects of intrinsic and innate immunity v0.91 IFNGR2 Zornitza Stark Phenotypes for gene: IFNGR2 were changed from to Immunodeficiency 28, mycobacteriosis, MIM# 614889
Defects of intrinsic and innate immunity v0.90 IFNGR2 Zornitza Stark Publications for gene: IFNGR2 were set to
Defects of intrinsic and innate immunity v0.89 IFNGR2 Zornitza Stark Mode of inheritance for gene: IFNGR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Defects of intrinsic and innate immunity v0.88 IFNGR2 Zornitza Stark reviewed gene: IFNGR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 15924140, 18625743, 31222290; Phenotypes: Immunodeficiency 28, mycobacteriosis, MIM# 614889; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11422 IFNGR2 Zornitza Stark Marked gene: IFNGR2 as ready
Mendeliome v0.11422 IFNGR2 Zornitza Stark Gene: ifngr2 has been classified as Green List (High Evidence).
Mendeliome v0.11422 IFNGR2 Zornitza Stark Phenotypes for gene: IFNGR2 were changed from to Immunodeficiency 28, mycobacteriosis, MIM# 614889
Mendeliome v0.11421 IFNGR2 Zornitza Stark Publications for gene: IFNGR2 were set to
Mendeliome v0.11420 IFNGR2 Zornitza Stark Mode of inheritance for gene: IFNGR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11419 IFNGR2 Zornitza Stark reviewed gene: IFNGR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 15924140, 18625743, 31222290; Phenotypes: Immunodeficiency 28, mycobacteriosis, MIM# 614889; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Defects of intrinsic and innate immunity v0.88 IFNGR1 Zornitza Stark Marked gene: IFNGR1 as ready
Defects of intrinsic and innate immunity v0.88 IFNGR1 Zornitza Stark Gene: ifngr1 has been classified as Green List (High Evidence).
Defects of intrinsic and innate immunity v0.88 IFNGR1 Zornitza Stark Phenotypes for gene: IFNGR1 were changed from to Immunodeficiency 27A, mycobacteriosis, AR, MIM# 209950; Immunodeficiency 27B, mycobacteriosis, AD, MIM# 615978
Defects of intrinsic and innate immunity v0.87 IFNGR1 Zornitza Stark Publications for gene: IFNGR1 were set to
Defects of intrinsic and innate immunity v0.86 IFNGR1 Zornitza Stark Mode of inheritance for gene: IFNGR1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Defects of intrinsic and innate immunity v0.85 IFNGR1 Zornitza Stark reviewed gene: IFNGR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 7815885, 8960475, 9389728, 10811850, 10192386, 12244188, 15589309; Phenotypes: Immunodeficiency 27A, mycobacteriosis, AR, MIM# 209950, Immunodeficiency 27B, mycobacteriosis, AD, MIM# 615978; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11419 IFNGR1 Zornitza Stark Marked gene: IFNGR1 as ready
Mendeliome v0.11419 IFNGR1 Zornitza Stark Gene: ifngr1 has been classified as Green List (High Evidence).
Mendeliome v0.11419 IFNGR1 Zornitza Stark Phenotypes for gene: IFNGR1 were changed from to Immunodeficiency 27A, mycobacteriosis, AR, MIM# 209950; Immunodeficiency 27B, mycobacteriosis, AD, MIM# 615978
Mendeliome v0.11418 IFNGR1 Zornitza Stark Publications for gene: IFNGR1 were set to
Mendeliome v0.11417 IFNGR1 Zornitza Stark Mode of inheritance for gene: IFNGR1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11416 IFNGR1 Zornitza Stark reviewed gene: IFNGR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 7815885, 8960475, 9389728, 10811850, 10192386, 12244188, 15589309; Phenotypes: Immunodeficiency 27A, mycobacteriosis, AR, MIM# 209950, Immunodeficiency 27B, mycobacteriosis, AD, MIM# 615978; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11416 IFITM3 Zornitza Stark Marked gene: IFITM3 as ready
Mendeliome v0.11416 IFITM3 Zornitza Stark Gene: ifitm3 has been classified as Red List (Low Evidence).
Mendeliome v0.11416 IFITM3 Zornitza Stark Phenotypes for gene: IFITM3 were changed from to {Influenza, severe, susceptibility to} 614680
Mendeliome v0.11415 IFITM3 Zornitza Stark Classified gene: IFITM3 as Red List (low evidence)
Mendeliome v0.11415 IFITM3 Zornitza Stark Gene: ifitm3 has been classified as Red List (Low Evidence).
Mendeliome v0.11414 IFITM3 Zornitza Stark reviewed gene: IFITM3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Influenza, severe, susceptibility to} 614680; Mode of inheritance: None
Amelogenesis imperfecta v1.3 DSPP Chirag Patel Classified gene: DSPP as Green List (high evidence)
Amelogenesis imperfecta v1.3 DSPP Chirag Patel Gene: dspp has been classified as Green List (High Evidence).
Amelogenesis imperfecta v1.2 DSPP Chirag Patel gene: DSPP was added
gene: DSPP was added to Amelogenesis imperfecta. Sources: Literature
Mode of inheritance for gene: DSPP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DSPP were set to PMID: 18456718, 11175779
Phenotypes for gene: DSPP were set to Dentinogenesis imperfecta, Shields type II, OMIM #125490
Review for gene: DSPP was set to GREEN
Added comment: Dentinogenesis imperfecta presents with blue-gray/amber brown and opalescent teeth, bulbous crowns, narrow roots, small/obliterated pulp chambers and root canals, and split enamel. Heterozygous mutations in DSPP gene identified in 5 families. Dspp knockout mice developed tooth defects similar to those of human DGI-III, including enlarged pulp chambers, increased width of predentin zone, hypomineralization, and pulp exposure
Sources: Literature
Mendeliome v0.11414 IDH3B Zornitza Stark Marked gene: IDH3B as ready
Mendeliome v0.11414 IDH3B Zornitza Stark Gene: idh3b has been classified as Green List (High Evidence).
Mendeliome v0.11414 IDH3B Zornitza Stark Phenotypes for gene: IDH3B were changed from to Retinitis pigmentosa 46, MIM# 612572
Mendeliome v0.11413 IDH3B Zornitza Stark Publications for gene: IDH3B were set to
Mendeliome v0.11412 IDH3B Zornitza Stark Mode of inheritance for gene: IDH3B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11411 IDH3B Zornitza Stark reviewed gene: IDH3B: Rating: GREEN; Mode of pathogenicity: None; Publications: 18806796, 31736247; Phenotypes: Retinitis pigmentosa 46, MIM# 612572; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11411 IDH2 Zornitza Stark Marked gene: IDH2 as ready
Mendeliome v0.11411 IDH2 Zornitza Stark Gene: idh2 has been classified as Green List (High Evidence).
Mendeliome v0.11411 IDH2 Zornitza Stark Phenotypes for gene: IDH2 were changed from to D-2-hydroxyglutaric aciduria 2, MIM# 613657
Mendeliome v0.11410 IDH2 Zornitza Stark Publications for gene: IDH2 were set to
Mendeliome v0.11409 IDH2 Zornitza Stark Mode of inheritance for gene: IDH2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11408 IDH2 Zornitza Stark reviewed gene: IDH2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25778941, 27142242, 20847235, 24049096; Phenotypes: D-2-hydroxyglutaric aciduria 2, MIM# 613657; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11408 ICOS Zornitza Stark Marked gene: ICOS as ready
Mendeliome v0.11408 ICOS Zornitza Stark Gene: icos has been classified as Green List (High Evidence).
Mendeliome v0.11408 ICOS Zornitza Stark Phenotypes for gene: ICOS were changed from to Immunodeficiency, common variable, 1 MIM# 607594
Mendeliome v0.11407 ICOS Zornitza Stark Publications for gene: ICOS were set to
Mendeliome v0.11406 ICOS Zornitza Stark Mode of inheritance for gene: ICOS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11405 ICOS Zornitza Stark reviewed gene: ICOS: Rating: GREEN; Mode of pathogenicity: None; Publications: 12577056, 15507387, 19380800, 28861081, 31858365, 11343122, 16982935; Phenotypes: Immunodeficiency, common variable, 1 MIM# 607594; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11405 ICAM4 Zornitza Stark Marked gene: ICAM4 as ready
Mendeliome v0.11405 ICAM4 Zornitza Stark Gene: icam4 has been classified as Red List (Low Evidence).
Mendeliome v0.11405 ICAM4 Zornitza Stark Phenotypes for gene: ICAM4 were changed from to [Blood group, Landsteiner-Wiener] 111250
Mendeliome v0.11404 ICAM4 Zornitza Stark Classified gene: ICAM4 as Red List (low evidence)
Mendeliome v0.11404 ICAM4 Zornitza Stark Gene: icam4 has been classified as Red List (Low Evidence).
Mendeliome v0.11403 ICAM4 Zornitza Stark reviewed gene: ICAM4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: [Blood group, Landsteiner-Wiener] 111250; Mode of inheritance: None
Mendeliome v0.11403 ACACA Zornitza Stark Marked gene: ACACA as ready
Mendeliome v0.11403 ACACA Zornitza Stark Gene: acaca has been classified as Red List (Low Evidence).
Mendeliome v0.11403 ACACA Zornitza Stark Phenotypes for gene: ACACA were changed from to Acetyl-CoA carboxylase deficiency MIM#613933
Mendeliome v0.11402 ACACA Zornitza Stark Publications for gene: ACACA were set to
Mendeliome v0.11401 ACACA Zornitza Stark Mode of inheritance for gene: ACACA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11400 ACACA Zornitza Stark Classified gene: ACACA as Red List (low evidence)
Mendeliome v0.11400 ACACA Zornitza Stark Gene: acaca has been classified as Red List (Low Evidence).
Mendeliome v0.11399 ABL1 Zornitza Stark Marked gene: ABL1 as ready
Mendeliome v0.11399 ABL1 Zornitza Stark Gene: abl1 has been classified as Green List (High Evidence).
Mendeliome v0.11399 ABCG8 Zornitza Stark Marked gene: ABCG8 as ready
Mendeliome v0.11399 ABCG8 Zornitza Stark Gene: abcg8 has been classified as Green List (High Evidence).
Mendeliome v0.11399 ABCG8 Zornitza Stark Phenotypes for gene: ABCG8 were changed from to Sitosterolemia 1, MIM#210250
Mendeliome v0.11398 ABCG8 Zornitza Stark Publications for gene: ABCG8 were set to
Mendeliome v0.11397 ABCG8 Zornitza Stark Mode of inheritance for gene: ABCG8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11396 C1QTNF5 Zornitza Stark Publications for gene: C1QTNF5 were set to
Mendeliome v0.11395 C1GALT1C1 Zornitza Stark Publications for gene: C1GALT1C1 were set to
Hydrops fetalis v0.221 MAPK1 Zornitza Stark Marked gene: MAPK1 as ready
Hydrops fetalis v0.221 MAPK1 Zornitza Stark Gene: mapk1 has been classified as Amber List (Moderate Evidence).
Hydrops fetalis v0.221 MAPK1 Zornitza Stark reviewed gene: MAPK1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Noonan syndrome 13 MIM#619087; Mode of inheritance: None
Macrocephaly_Megalencephaly v0.103 TET3 Zornitza Stark Marked gene: TET3 as ready
Macrocephaly_Megalencephaly v0.103 TET3 Zornitza Stark Gene: tet3 has been classified as Amber List (Moderate Evidence).
Macrocephaly_Megalencephaly v0.103 TET3 Zornitza Stark Classified gene: TET3 as Amber List (moderate evidence)
Macrocephaly_Megalencephaly v0.103 TET3 Zornitza Stark Gene: tet3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11394 ACACA Elena Savva reviewed gene: ACACA: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 34552920, 10677481, 16717184; Phenotypes: Acetyl-CoA carboxylase deficiency MIM#613933; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11394 ACAD8 Elena Savva Marked gene: ACAD8 as ready
Mendeliome v0.11394 ACAD8 Elena Savva Gene: acad8 has been classified as Green List (High Evidence).
Mendeliome v0.11394 ACAD8 Elena Savva Publications for gene: ACAD8 were set to
Mendeliome v0.11394 C2 Ain Roesley Phenotypes for gene: C2 were changed from C2 deficiency MIM#217000 to C2 deficiency MIM#217000
Mendeliome v0.11394 C2 Ain Roesley Publications for gene: C2 were set to 16026838; 8621452; 35272074; 32385807
Mendeliome v0.11393 ACAD8 Elena Savva Mode of inheritance for gene: ACAD8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11392 ACAD8 Elena Savva reviewed gene: ACAD8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34544473; Phenotypes: Isobutyryl-CoA dehydrogenase deficiency MIM#611283; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11392 C2 Ain Roesley Phenotypes for gene: C2 were changed from to C2 deficiency MIM#217000
Mendeliome v0.11391 C2 Ain Roesley Publications for gene: C2 were set to
Mendeliome v0.11391 C2 Ain Roesley Marked gene: C2 as ready
Mendeliome v0.11391 C2 Ain Roesley Gene: c2 has been classified as Green List (High Evidence).
Mendeliome v0.11391 C2 Ain Roesley Mode of inheritance for gene: C2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11390 C2 Ain Roesley edited their review of gene: C2: Changed rating: GREEN
Mendeliome v0.11390 ABL1 Elena Savva Phenotypes for gene: ABL1 were changed from to Congenital heart defects and skeletal malformations syndrome MIM#617602
Mendeliome v0.11389 ABL1 Elena Savva Mode of pathogenicity for gene: ABL1 was changed from to Other
Mendeliome v0.11389 ABL1 Elena Savva Publications for gene: ABL1 were set to
Mendeliome v0.11389 ABL1 Elena Savva Mode of inheritance for gene: ABL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.11388 ABL1 Elena Savva reviewed gene: ABL1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 28288113, 30855488, 32643838; Phenotypes: Congenital heart defects and skeletal malformations syndrome MIM#617602; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.11388 ABCG8 Elena Savva reviewed gene: ABCG8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Sitosterolemia 1 MIM#210250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11388 C2 Ain Roesley reviewed gene: C2: Rating: ; Mode of pathogenicity: None; Publications: 16026838, 8621452, 35272074, 32385807; Phenotypes: C2 deficiency MIM#217000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Complement Deficiencies v0.47 C1S Ain Roesley Phenotypes for gene: C1S were changed from to C1s deficiency MIM#613783
Complement Deficiencies v0.47 C1S Ain Roesley Publications for gene: C1S were set to
Complement Deficiencies v0.47 C1S Ain Roesley Mode of inheritance for gene: C1S was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Complement Deficiencies v0.46 C1S Ain Roesley Marked gene: C1S as ready
Complement Deficiencies v0.46 C1S Ain Roesley Gene: c1s has been classified as Green List (High Evidence).
Complement Deficiencies v0.46 C1S Ain Roesley reviewed gene: C1S: Rating: GREEN; Mode of pathogenicity: None; Publications: 19155518, 20191570, 18062908, 11390518, 9856483; Phenotypes: C1s deficiency MIM#613783; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11388 C1S Ain Roesley Phenotypes for gene: C1S were changed from to Ehlers-Danlos syndrome, periodontal type, 2 MIM#617174; C1s deficiency MIM#613783
Mendeliome v0.11387 C1S Ain Roesley Publications for gene: C1S were set to
Mendeliome v0.11387 C1S Ain Roesley Marked gene: C1S as ready
Mendeliome v0.11387 C1S Ain Roesley Gene: c1s has been classified as Green List (High Evidence).
Mendeliome v0.11387 C1S Ain Roesley Mode of inheritance for gene: C1S was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11386 C1S Ain Roesley reviewed gene: C1S: Rating: GREEN; Mode of pathogenicity: None; Publications: 28306229, 30071989, 27745832, 31921203, 19155518, 20191570, 18062908, 11390518, 9856483; Phenotypes: Ehlers-Danlos syndrome, periodontal type, 2 MIM#617174, C1s deficiency MIM#613783; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Aortopathy_Connective Tissue Disorders v1.66 C1S Ain Roesley Publications for gene: C1S were set to 30071989; 27745832; 31921203; 28306229
Mendeliome v0.11386 ABCC8 Elena Savva Marked gene: ABCC8 as ready
Mendeliome v0.11386 ABCC8 Elena Savva Gene: abcc8 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v1.66 C1S Ain Roesley edited their review of gene: C1S: Changed rating: GREEN; Changed publications: 30071989, 27745832, 31921203, 28306229; Changed phenotypes: Ehlers-Danlos syndrome, periodontal type, 2 MIM#617174; Set current diagnostic: yes
Aortopathy_Connective Tissue Disorders v1.66 C1S Ain Roesley Phenotypes for gene: C1S were changed from Ehlers-Danlos syndrome, periodontal type, 1 (MIM# 130080) to Ehlers-Danlos syndrome, periodontal type, 2 MIM#617174
Aortopathy_Connective Tissue Disorders v1.65 C1S Ain Roesley Classified gene: C1S as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v1.65 C1S Ain Roesley Gene: c1s has been classified as Green List (High Evidence).
Mendeliome v0.11386 ABCC8 Elena Savva Phenotypes for gene: ABCC8 were changed from to Diabetes mellitus, noninsulin-dependent MIM#125853; Diabetes mellitus, permanent neonatal 3, with or without neurologic features MIM#618857; Diabetes mellitus, transient neonatal 2 MIM#610374; Hyperinsulinemic hypoglycemia, familial, 1 MIM#256450; Hypoglycemia of infancy, leucine-sensitive MIM#240800
Mendeliome v0.11385 ABCC8 Elena Savva Publications for gene: ABCC8 were set to
Mendeliome v0.11385 ABCC8 Elena Savva Mode of inheritance for gene: ABCC8 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11384 ABCC8 Elena Savva reviewed gene: ABCC8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 21054355, 32027066, 32376986; Phenotypes: Diabetes mellitus, noninsulin-dependent MIM#125853, Diabetes mellitus, permanent neonatal 3, with or without neurologic features MIM#618857, Diabetes mellitus, transient neonatal 2 MIM#610374, Hyperinsulinemic hypoglycemia, familial, 1 MIM#256450, Hypoglycemia of infancy, leucine-sensitive MIM#240800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11384 C1R Ain Roesley Marked gene: C1R as ready
Mendeliome v0.11384 C1R Ain Roesley Gene: c1r has been classified as Green List (High Evidence).
Mendeliome v0.11384 C1R Ain Roesley Phenotypes for gene: C1R were changed from to Ehlers-Danlos syndrome, periodontal type, 1 MIM# 130080 Current Edit
Mendeliome v0.11383 C1R Ain Roesley Publications for gene: C1R were set to
Mendeliome v0.11383 C1R Ain Roesley Mode of inheritance for gene: C1R was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11382 ITCH Zornitza Stark Marked gene: ITCH as ready
Mendeliome v0.11382 ITCH Zornitza Stark Gene: itch has been classified as Green List (High Evidence).
Mendeliome v0.11382 C1R Ain Roesley reviewed gene: C1R: Rating: GREEN; Mode of pathogenicity: None; Publications: 27745832, 28306229; Phenotypes: Ehlers-Danlos syndrome, periodontal type, 1 MIM# 130080; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.11382 ITCH Zornitza Stark Phenotypes for gene: ITCH were changed from to Autoimmune disease, multisystem, with facial dysmorphism, MIM#613385
Mendeliome v0.11381 ITCH Zornitza Stark Publications for gene: ITCH were set to
Mendeliome v0.11380 C1QTNF5 Ain Roesley Phenotypes for gene: C1QTNF5 were changed from to Retinal degeneration, late-onset, autosomal dominant MIM#605670
Mendeliome v0.11379 C1QTNF5 Ain Roesley Marked gene: C1QTNF5 as ready
Mendeliome v0.11380 C1QTNF5 Ain Roesley Publications for gene: C1QTNF5 were set to
Mendeliome v0.11379 C1QTNF5 Ain Roesley Gene: c1qtnf5 has been classified as Green List (High Evidence).
Mendeliome v0.11379 ITCH Zornitza Stark Mode of inheritance for gene: ITCH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4572 ITCH Zornitza Stark Publications for gene: ITCH were set to 20170897
Mendeliome v0.11378 ITCH Zornitza Stark Tag founder tag was added to gene: ITCH.
Intellectual disability syndromic and non-syndromic v0.4571 ITCH Zornitza Stark edited their review of gene: ITCH: Added comment: Unrelated individual reported in PMID 31091003 had normal intellect.; Changed publications: 20170897, 31091003
Mendeliome v0.11378 C1QTNF5 Ain Roesley Mode of pathogenicity for gene: C1QTNF5 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 v0.11378 C1QTNF5 Ain Roesley Mode of inheritance for gene: C1QTNF5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11377 ITCH Zornitza Stark reviewed gene: ITCH: Rating: GREEN; Mode of pathogenicity: None; Publications: 20170897, 31091003, 32356405; Phenotypes: Autoimmune disease, multisystem, with facial dysmorphism, MIM#613385; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11377 C1QTNF5 Ain Roesley reviewed gene: C1QTNF5: 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: 33949280, 12944416, 30451557, 28939808, : 32036094; Phenotypes: Retinal degeneration, late-onset, autosomal dominant MIM#605670; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.11377 ITGA7 Zornitza Stark Marked gene: ITGA7 as ready
Mendeliome v0.11377 ITGA7 Zornitza Stark Gene: itga7 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.99 ITGA7 Zornitza Stark Marked gene: ITGA7 as ready
Muscular dystrophy and myopathy_Paediatric v0.99 ITGA7 Zornitza Stark Gene: itga7 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.99 ITGA7 Zornitza Stark Phenotypes for gene: ITGA7 were changed from to Muscular dystrophy, congenital, due to ITGA7 deficiency, MIM# 613204
Muscular dystrophy and myopathy_Paediatric v0.98 ITGA7 Zornitza Stark Publications for gene: ITGA7 were set to
Muscular dystrophy and myopathy_Paediatric v0.97 ITGA7 Zornitza Stark Mode of inheritance for gene: ITGA7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.96 ITGA7 Zornitza Stark reviewed gene: ITGA7: Rating: GREEN; Mode of pathogenicity: None; Publications: 34552617, 9590299; Phenotypes: Muscular dystrophy, congenital, due to ITGA7 deficiency, MIM# 613204; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11377 ITGA7 Zornitza Stark Phenotypes for gene: ITGA7 were changed from to Muscular dystrophy, congenital, due to ITGA7 deficiency, MIM# 613204
Mendeliome v0.11376 ITGA7 Zornitza Stark Publications for gene: ITGA7 were set to
Mendeliome v0.11375 ITGA7 Zornitza Stark Mode of inheritance for gene: ITGA7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11374 ITGA7 Zornitza Stark reviewed gene: ITGA7: Rating: GREEN; Mode of pathogenicity: None; Publications: 34552617, 9590299; Phenotypes: Muscular dystrophy, congenital, due to ITGA7 deficiency, MIM# 613204; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4571 ITPA Zornitza Stark Marked gene: ITPA as ready
Intellectual disability syndromic and non-syndromic v0.4571 ITPA Zornitza Stark Gene: itpa has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4571 ITPA Zornitza Stark Phenotypes for gene: ITPA were changed from to Developmental and epileptic encephalopathy 35, MIM# 616647
Intellectual disability syndromic and non-syndromic v0.4570 ITPA Zornitza Stark Publications for gene: ITPA were set to
Intellectual disability syndromic and non-syndromic v0.4569 ITPA Zornitza Stark Mode of inheritance for gene: ITPA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4568 ITPA Zornitza Stark reviewed gene: ITPA: Rating: GREEN; Mode of pathogenicity: None; Publications: 26224535, 19498443, 35234647, 35098521; Phenotypes: Developmental and epileptic encephalopathy 35, MIM# 616647; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11374 C1QC Ain Roesley Phenotypes for gene: C1QC were changed from to C1q deficiency MIM#613652
Mendeliome v0.11373 C1QC Ain Roesley Publications for gene: C1QC were set to
Mendeliome v0.11373 C1QC Ain Roesley Marked gene: C1QC as ready
Mendeliome v0.11373 C1QC Ain Roesley Gene: c1qc has been classified as Green List (High Evidence).
Mendeliome v0.11373 C1QC Ain Roesley Mode of inheritance for gene: C1QC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11372 ITPA Zornitza Stark Marked gene: ITPA as ready
Mendeliome v0.11372 ITPA Zornitza Stark Gene: itpa has been classified as Green List (High Evidence).
Mendeliome v0.11372 C1QC Ain Roesley reviewed gene: C1QC: Rating: GREEN; Mode of pathogenicity: None; Publications: 21654842, 8630118, 24157463; Phenotypes: C1q deficiency MIM#613652; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11372 ITPA Zornitza Stark Phenotypes for gene: ITPA were changed from to Inosine triphosphatase deficiency MIM#613850; Developmental and epileptic encephalopathy 35 MIM#616647
Mendeliome v0.11371 ITPA Zornitza Stark Publications for gene: ITPA were set to
Complement Deficiencies v0.46 C1QC Ain Roesley edited their review of gene: C1QC: Changed publications: 21654842, 8630118, 24157463
Mendeliome v0.11370 ITPA Zornitza Stark reviewed gene: ITPA: Rating: GREEN; Mode of pathogenicity: None; Publications: 26224535, 19498443, 35234647, 35098521; Phenotypes: Developmental and epileptic encephalopathy 35, MIM# 616647; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Complement Deficiencies v0.46 C1QC Ain Roesley Marked gene: C1QC as ready
Complement Deficiencies v0.46 C1QC Ain Roesley Gene: c1qc has been classified as Green List (High Evidence).
Complement Deficiencies v0.46 C1QC Ain Roesley Publications for gene: C1QC were set to
Complement Deficiencies v0.45 C1QC Ain Roesley Phenotypes for gene: C1QC were changed from to C1q deficiency MIM#613652
Complement Deficiencies v0.45 C1QC Ain Roesley Mode of inheritance for gene: C1QC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Complement Deficiencies v0.44 C1QC Ain Roesley reviewed gene: C1QC: Rating: GREEN; Mode of pathogenicity: None; Publications: 8630118; Phenotypes: C1q deficiency MIM#613652; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11370 ITPA Zornitza Stark Mode of inheritance for gene: ITPA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Hyperammonaemia v0.4 IVD Zornitza Stark Marked gene: IVD as ready
Hyperammonaemia v0.4 IVD Zornitza Stark Gene: ivd has been classified as Green List (High Evidence).
Hyperammonaemia v0.4 IVD Zornitza Stark Phenotypes for gene: IVD were changed from Isovaleric acidemia 243500 to Isovaleric acidaemia, MIM# 243500
Hyperammonaemia v0.3 IVD Zornitza Stark Publications for gene: IVD were set to 23063737; 26018748; 24019846; 23587913
Hyperammonaemia v0.2 IVD Zornitza Stark reviewed gene: IVD: Rating: GREEN; Mode of pathogenicity: None; Publications: 15486829; Phenotypes: Isovaleric acidaemia, MIM# 243500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11369 IVD Zornitza Stark Marked gene: IVD as ready
Mendeliome v0.11369 IVD Zornitza Stark Gene: ivd has been classified as Green List (High Evidence).
Mendeliome v0.11369 IVD Zornitza Stark Phenotypes for gene: IVD were changed from to Isovaleric acidaemia, MIM# 243500
Mendeliome v0.11368 IVD Zornitza Stark Publications for gene: IVD were set to
Mendeliome v0.11367 IVD Zornitza Stark Mode of inheritance for gene: IVD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11366 IVD Zornitza Stark reviewed gene: IVD: Rating: GREEN; Mode of pathogenicity: None; Publications: 15486829; Phenotypes: Isovaleric acidaemia, MIM# 243500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11366 C1QB Ain Roesley Publications for gene: C1QB were set to
Mendeliome v0.11366 C1QB Ain Roesley Phenotypes for gene: C1QB were changed from to C1q deficiency, MIM# 613652
Mendeliome v0.11366 C1QB Ain Roesley Mode of inheritance for gene: C1QB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11365 C1QB Ain Roesley Marked gene: C1QB as ready
Mendeliome v0.11365 C1QB Ain Roesley Gene: c1qb has been classified as Green List (High Evidence).
Mendeliome v0.11365 C1QB Ain Roesley reviewed gene: C1QB: Rating: GREEN; Mode of pathogenicity: None; Publications: 2894352, 17513176; Phenotypes: C1q deficiency, MIM# 613652; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Hydrocephalus_Ventriculomegaly v0.112 C12orf57 Ain Roesley Marked gene: C12orf57 as ready
Hydrocephalus_Ventriculomegaly v0.112 C12orf57 Ain Roesley Gene: c12orf57 has been classified as Green List (High Evidence).
Mendeliome v0.11365 IYD Zornitza Stark Marked gene: IYD as ready
Mendeliome v0.11365 IYD Zornitza Stark Gene: iyd has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4568 C12orf57 Ain Roesley Marked gene: C12orf57 as ready
Intellectual disability syndromic and non-syndromic v0.4568 C12orf57 Ain Roesley Gene: c12orf57 has been classified as Green List (High Evidence).
Mendeliome v0.11365 IYD Zornitza Stark Phenotypes for gene: IYD were changed from to Thyroid dyshormonogenesis 4, MIM# 274800
Mendeliome v0.11364 C12orf57 Ain Roesley Marked gene: C12orf57 as ready
Mendeliome v0.11364 C12orf57 Ain Roesley Gene: c12orf57 has been classified as Green List (High Evidence).
Mendeliome v0.11364 C12orf4 Ain Roesley Marked gene: C12orf4 as ready
Mendeliome v0.11364 C12orf4 Ain Roesley Gene: c12orf4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4568 C12orf4 Ain Roesley Marked gene: C12orf4 as ready
Intellectual disability syndromic and non-syndromic v0.4568 C12orf4 Ain Roesley Gene: c12orf4 has been classified as Green List (High Evidence).
Mendeliome v0.11364 IYD Zornitza Stark Publications for gene: IYD were set to
Mendeliome v0.11363 IYD Zornitza Stark Mode of inheritance for gene: IYD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11362 C1GALT1C1 Ain Roesley Marked gene: C1GALT1C1 as ready
Mendeliome v0.11362 C1GALT1C1 Ain Roesley Gene: c1galt1c1 has been classified as Green List (High Evidence).
Red cell disorders v1.11 C1GALT1C1 Ain Roesley Marked gene: C1GALT1C1 as ready
Red cell disorders v1.11 C1GALT1C1 Ain Roesley Gene: c1galt1c1 has been classified as Green List (High Evidence).
Mendeliome v0.11362 IYD Zornitza Stark changed review comment from: Four unrelated families reported.; to: Four unrelated families reported in 2008, limited reports since.
Mendeliome v0.11362 IYD Zornitza Stark reviewed gene: IYD: Rating: GREEN; Mode of pathogenicity: None; Publications: 18434651, 18434651; Phenotypes: Thyroid dyshormonogenesis 4, MIM# 274800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11362 C1GALT1C1 Ain Roesley Phenotypes for gene: C1GALT1C1 were changed from to Tn polyagglutination syndrome, somatic MIM#300622
Red cell disorders v1.11 C1GALT1C1 Ain Roesley Phenotypes for gene: C1GALT1C1 were changed from to Tn polyagglutination syndrome, somatic MIM#300622
Red cell disorders v1.10 C1GALT1C1 Ain Roesley Classified gene: C1GALT1C1 as Green List (high evidence)
Red cell disorders v1.10 C1GALT1C1 Ain Roesley Gene: c1galt1c1 has been classified as Green List (High Evidence).
Red cell disorders v1.9 C1GALT1C1 Ain Roesley gene: C1GALT1C1 was added
gene: C1GALT1C1 was added to Red cell disorders. Sources: Literature
somatic tags were added to gene: C1GALT1C1.
Mode of inheritance for gene: C1GALT1C1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: C1GALT1C1 were set to 18537974; 16251947
Review for gene: C1GALT1C1 was set to GREEN
gene: C1GALT1C1 was marked as current diagnostic
Added comment: Previously known as COSMC
>3 unrelated. In 1 female, she was heterozygous for the variant in whole blood but homozygous in erythroblast culture
Sources: Literature
Mendeliome v0.11361 C1GALT1C1 Ain Roesley Mode of inheritance for gene: C1GALT1C1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.11360 C1GALT1C1 Ain Roesley reviewed gene: C1GALT1C1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18537974, 16251947; Phenotypes: Tn polyagglutination syndrome, somatic MIM#300622; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Fetal anomalies v1.11 SCAF4 Zornitza Stark Marked gene: SCAF4 as ready
Fetal anomalies v1.11 SCAF4 Zornitza Stark Gene: scaf4 has been classified as Green List (High Evidence).
Fetal anomalies v1.11 SCAF4 Zornitza Stark Phenotypes for gene: SCAF4 were changed from Neurodevelopmental disorder, SCAF4-related MONDO#0700092 to Neurodevelopmental disorder MONDO#0700092, SCAF4-related
Fetal anomalies v1.10 SCAF4 Zornitza Stark Classified gene: SCAF4 as Green List (high evidence)
Fetal anomalies v1.10 SCAF4 Zornitza Stark Gene: scaf4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4568 C12orf57 Ain Roesley Phenotypes for gene: C12orf57 were changed from to Temtamy syndrome MIM#218340
Intellectual disability syndromic and non-syndromic v0.4568 C12orf57 Ain Roesley Mode of inheritance for gene: C12orf57 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4568 C12orf57 Ain Roesley Publications for gene: C12orf57 were set to
Intellectual disability syndromic and non-syndromic v0.4567 C12orf57 Ain Roesley reviewed gene: C12orf57: Rating: GREEN; Mode of pathogenicity: None; Publications: 29383837, 31853307; Phenotypes: Temtamy syndrome MIM#218340; Mode of inheritance: None; Current diagnostic: yes
Hydrocephalus_Ventriculomegaly v0.112 C12orf57 Ain Roesley Classified gene: C12orf57 as Green List (high evidence)
Hydrocephalus_Ventriculomegaly v0.112 C12orf57 Ain Roesley Gene: c12orf57 has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.111 C12orf57 Ain Roesley gene: C12orf57 was added
gene: C12orf57 was added to Hydrocephalus_Ventriculomegaly. Sources: Literature
Mode of inheritance for gene: C12orf57 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C12orf57 were set to 29383837; 31853307
Phenotypes for gene: C12orf57 were set to Temtamy syndrome MIM#218340
Penetrance for gene: C12orf57 were set to Complete
Review for gene: C12orf57 was set to GREEN
gene: C12orf57 was marked as current diagnostic
Added comment: 17/50 individuals reported with ventriculomegaly
Sources: Literature
Hydrops fetalis v0.221 MAPK1 Elena Savva Classified gene: MAPK1 as Amber List (moderate evidence)
Hydrops fetalis v0.221 MAPK1 Elena Savva Gene: mapk1 has been classified as Amber List (Moderate Evidence).
Hydrops fetalis v0.221 MAPK1 Elena Savva Classified gene: MAPK1 as Amber List (moderate evidence)
Hydrops fetalis v0.221 MAPK1 Elena Savva Gene: mapk1 has been classified as Amber List (Moderate Evidence).
Hydrops fetalis v0.220 MAPK1 Elena Savva gene: MAPK1 was added
gene: MAPK1 was added to Hydrops fetalis. Sources: Literature
Mode of inheritance for gene: MAPK1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MAPK1 were set to PMID: 32721402
Phenotypes for gene: MAPK1 were set to Noonan syndrome 13 MIM#619087
Review for gene: MAPK1 was set to GREEN
Added comment: PMID: 32721402 - GOF de novo missense variants reported in Noonan patients. Patients showed DD, ID, craniofacial abnormalities and CHD

Supported by K/I mouse model
Sources: Literature
Fetal anomalies v1.9 SCAF4 Lucy Spencer gene: SCAF4 was added
gene: SCAF4 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SCAF4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SCAF4 were set to PMID: 32730804
Phenotypes for gene: SCAF4 were set to Neurodevelopmental disorder, SCAF4-related MONDO#0700092
Review for gene: SCAF4 was set to GREEN
Added comment: PMID: 32730804- 11 individuals with SCAF4 variants, 9 are de novo. Present with mild to severe ID/Dev delay, most have seizures, 4 have cardiac defects, 4 have renal anomalies, 3 have urogenital anomalies, 6 have skeletal anomalies, 2 have GI anomalies.
Sources: Literature
Macrocephaly_Megalencephaly v0.102 TET3 Elena Savva changed review comment from: PMID: 31928709 - 11 cases in 8 families.
3/11 had true macrocephaly (>2 SD above), 1/11 had borderline and relative macrocephaly.
Of the three with true macrocephaly, 1/3 had AR disease accompanied by tall stature, 2/3 had AD de novo variants. The borderline and relative macrocephaly patient was also for AD disease

However 2/11 patients (siblings) had microcephaly
Sources: Literature; to: PMID: 31928709 - 11 cases in 8 families.
3/11 had true macrocephaly (>2 SD above), 1/11 had borderline and relative macrocephaly.
Of the three with true macrocephaly, 1/3 had AR disease accompanied by tall stature, 2/3 had AD de novo variants. The borderline and relative macrocephaly patient was also for AD disease

However 2/11 patients (siblings) had microcephaly
Sources: Literature
Macrocephaly_Megalencephaly v0.102 TET3 Elena Savva gene: TET3 was added
gene: TET3 was added to Macrocephaly_Megalencephaly. Sources: Literature
Mode of inheritance for gene: TET3 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: TET3 were set to PMID: 31928709
Phenotypes for gene: TET3 were set to Beck-Fahrner syndrome MIM#618798
Review for gene: TET3 was set to AMBER
Added comment: PMID: 31928709 - 11 cases in 8 families.
3/11 had true macrocephaly (>2 SD above), 1/11 had borderline and relative macrocephaly.
Of the three with true macrocephaly, 1/3 had AR disease accompanied by tall stature, 2/3 had AD de novo variants. The borderline and relative macrocephaly patient was also for AD disease

However 2/11 patients (siblings) had microcephaly
Sources: Literature
Mendeliome v0.11360 C12orf57 Ain Roesley Phenotypes for gene: C12orf57 were changed from to Temtamy syndrome MIM#218340
Mendeliome v0.11359 C12orf57 Ain Roesley Publications for gene: C12orf57 were set to
Mendeliome v0.11359 C12orf57 Ain Roesley Mode of inheritance for gene: C12orf57 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11358 C12orf57 Ain Roesley reviewed gene: C12orf57: Rating: GREEN; Mode of pathogenicity: None; Publications: 29383837, 31853307; Phenotypes: Temtamy syndrome MIM#218340; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.4567 C12orf4 Ain Roesley Phenotypes for gene: C12orf4 were changed from to Intellectual developmental disorder, autosomal recessive 66 MIM#618221
Intellectual disability syndromic and non-syndromic v0.4566 C12orf4 Ain Roesley Publications for gene: C12orf4 were set to 34967075; 31334606; 27311568; 25558065; 28097321
Intellectual disability syndromic and non-syndromic v0.4566 C12orf4 Ain Roesley Publications for gene: C12orf4 were set to 34967075; 31334606; 27311568; 25558065; 28097321
Mendeliome v0.11358 C12orf4 Ain Roesley Phenotypes for gene: C12orf4 were changed from to Intellectual developmental disorder, autosomal recessive 66 MIM#618221
Intellectual disability syndromic and non-syndromic v0.4565 C12orf4 Ain Roesley Publications for gene: C12orf4 were set to
Intellectual disability syndromic and non-syndromic v0.4565 C12orf4 Ain Roesley Mode of pathogenicity for gene: C12orf4 was changed from to None
Intellectual disability syndromic and non-syndromic v0.4564 C12orf4 Ain Roesley Mode of inheritance for gene: C12orf4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4563 C12orf4 Ain Roesley reviewed gene: C12orf4: Rating: GREEN; Mode of pathogenicity: None; Publications: 34967075, 31334606, 27311568, 25558065, 28097321; Phenotypes: Intellectual developmental disorder, autosomal recessive 66 MIM#618221; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11357 C12orf4 Ain Roesley Publications for gene: C12orf4 were set to
Mendeliome v0.11356 C12orf4 Ain Roesley Mode of pathogenicity for gene: C12orf4 was changed from to None
Mendeliome v0.11355 C12orf4 Ain Roesley Mode of inheritance for gene: C12orf4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11354 C12orf4 Ain Roesley reviewed gene: C12orf4: Rating: GREEN; Mode of pathogenicity: None; Publications: 34967075, 31334606, 27311568, 25558065, 28097321; Phenotypes: Intellectual developmental disorder, autosomal recessive 66 MIM#618221; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11354 IARS2 Zornitza Stark Marked gene: IARS2 as ready
Mendeliome v0.11354 IARS2 Zornitza Stark Gene: iars2 has been classified as Green List (High Evidence).
Mendeliome v0.11354 IARS2 Zornitza Stark Phenotypes for gene: IARS2 were changed from to Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, MIM# 616007
Mendeliome v0.11353 IARS2 Zornitza Stark Publications for gene: IARS2 were set to
Mendeliome v0.11352 IARS2 Zornitza Stark Mode of inheritance for gene: IARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11351 IARS2 Zornitza Stark reviewed gene: IARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 28328135, 30419932, 25130867, 30041933; Phenotypes: Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, MIM# 616007; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11351 KAAG1 Zornitza Stark Marked gene: KAAG1 as ready
Mendeliome v0.11351 KAAG1 Zornitza Stark Gene: kaag1 has been classified as Red List (Low Evidence).
Mendeliome v0.11351 KAAG1 Zornitza Stark Classified gene: KAAG1 as Red List (low evidence)
Mendeliome v0.11351 KAAG1 Zornitza Stark Gene: kaag1 has been classified as Red List (Low Evidence).
Mendeliome v0.11350 KAAG1 Zornitza Stark reviewed gene: KAAG1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.11350 KATNAL2 Zornitza Stark Marked gene: KATNAL2 as ready
Mendeliome v0.11350 KATNAL2 Zornitza Stark Gene: katnal2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11350 KATNAL2 Zornitza Stark Phenotypes for gene: KATNAL2 were changed from to Oligo-astheno-teratozoospermia; Autism
Mendeliome v0.11349 KATNAL2 Zornitza Stark Publications for gene: KATNAL2 were set to
Mendeliome v0.11348 KATNAL2 Zornitza Stark Mode of inheritance for gene: KATNAL2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11347 KATNAL2 Zornitza Stark Classified gene: KATNAL2 as Amber List (moderate evidence)
Mendeliome v0.11347 KATNAL2 Zornitza Stark Gene: katnal2 has been classified as Amber List (Moderate Evidence).
Autism v0.170 KATNAL2 Zornitza Stark Classified gene: KATNAL2 as Amber List (moderate evidence)
Autism v0.170 KATNAL2 Zornitza Stark Gene: katnal2 has been classified as Amber List (Moderate Evidence).
Autism v0.169 KATNAL2 Zornitza Stark edited their review of gene: KATNAL2: Changed rating: AMBER
Mendeliome v0.11346 KATNAL2 Zornitza Stark reviewed gene: KATNAL2: Rating: AMBER; Mode of pathogenicity: None; Publications: 34096614, 22495311, 21572417, 22495309, 22495306; Phenotypes: Oligo-astheno-teratozoospermia, Autism; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11346 KCNA1 Zornitza Stark Marked gene: KCNA1 as ready
Mendeliome v0.11346 KCNA1 Zornitza Stark Gene: kcna1 has been classified as Green List (High Evidence).
Mendeliome v0.11346 KCNA1 Zornitza Stark Phenotypes for gene: KCNA1 were changed from to Episodic ataxia/myokymia syndrome, MIM# 160120; Epilepsy, MONDO:0005027, KCNA1-related
Mendeliome v0.11345 KCNA1 Zornitza Stark Publications for gene: KCNA1 were set to
Mendeliome v0.11344 KCNA1 Zornitza Stark Mode of pathogenicity for gene: KCNA1 was changed from to None
Mendeliome v0.11343 KCNA1 Zornitza Stark Mode of inheritance for gene: KCNA1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11342 KCNA1 Zornitza Stark reviewed gene: KCNA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32316562; Phenotypes: Epilepsy, MONDO:0005027, KCNA1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11342 KCNA5 Zornitza Stark Marked gene: KCNA5 as ready
Mendeliome v0.11342 KCNA5 Zornitza Stark Gene: kcna5 has been classified as Green List (High Evidence).
Mendeliome v0.11342 KCNA5 Zornitza Stark Phenotypes for gene: KCNA5 were changed from to Atrial fibrillation, familial, 7, MIM# 612240
Mendeliome v0.11341 KCNA5 Zornitza Stark Publications for gene: KCNA5 were set to
Mendeliome v0.11340 KCNA5 Zornitza Stark Mode of inheritance for gene: KCNA5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11339 KCNA5 Zornitza Stark edited their review of gene: KCNA5: Changed rating: GREEN
Mendeliome v0.11339 KCNA5 Zornitza Stark reviewed gene: KCNA5: Rating: ; Mode of pathogenicity: None; Publications: 16772329, 19343045, 23264583; Phenotypes: Atrial fibrillation, familial, 7, MIM# 612240; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1481 KCND3 Zornitza Stark Marked gene: KCND3 as ready
Genetic Epilepsy v0.1481 KCND3 Zornitza Stark Gene: kcnd3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1481 KCND3 Zornitza Stark Classified gene: KCND3 as Green List (high evidence)
Genetic Epilepsy v0.1481 KCND3 Zornitza Stark Gene: kcnd3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1480 KCND3 Zornitza Stark gene: KCND3 was added
gene: KCND3 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: KCND3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCND3 were set to 32823520
Phenotypes for gene: KCND3 were set to Spinocerebellar ataxia 19, MIM#607346
Review for gene: KCND3 was set to GREEN
Added comment: Over 60 individuals reported with neurological disorders and variants in KCND3. Two broad clinical groups in terms of presentation: neurodevelopmental disorder with epilepsy and/or movement disorders with ataxia later in the disease course characterized the early onset forms, while a prominent ataxic syndrome with possible cognitive decline, movement disorders, and peripheral neuropathy were observed in the late onset forms.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.4563 KCND3 Zornitza Stark Publications for gene: KCND3 were set to
Mendeliome v0.11339 KCND3 Zornitza Stark Marked gene: KCND3 as ready
Mendeliome v0.11339 KCND3 Zornitza Stark Gene: kcnd3 has been classified as Green List (High Evidence).
Ataxia v0.328 KCND3 Zornitza Stark Marked gene: KCND3 as ready
Ataxia v0.328 KCND3 Zornitza Stark Gene: kcnd3 has been classified as Green List (High Evidence).
Ataxia v0.328 KCND3 Zornitza Stark Classified gene: KCND3 as Green List (high evidence)
Ataxia v0.328 KCND3 Zornitza Stark Gene: kcnd3 has been classified as Green List (High Evidence).
Ataxia v0.327 KCND3 Zornitza Stark gene: KCND3 was added
gene: KCND3 was added to Ataxia - paediatric. Sources: Expert Review
Mode of inheritance for gene: KCND3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCND3 were set to 32823520
Phenotypes for gene: KCND3 were set to Spinocerebellar ataxia 19, MIM# 607346
Review for gene: KCND3 was set to GREEN
Added comment: Variable age of symptom onset, including paediatric. Reviewed in PMID 32823520.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.4562 KCND3 Zornitza Stark Classified gene: KCND3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4562 KCND3 Zornitza Stark Gene: kcnd3 has been classified as Green List (High Evidence).
Atrial Fibrillation v0.12 KCNE5 Zornitza Stark Marked gene: KCNE5 as ready
Atrial Fibrillation v0.12 KCNE5 Zornitza Stark Gene: kcne5 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.4561 KCND3 Zornitza Stark changed review comment from: Progressive neurological condition; ID only reported in some, most however reported as having normal cognition.; to: Progressive neurological condition; ID only reported in some. Recent review of all published patients, PMID 32823520 defined a group with early onset of disease, where DD/ID are the predominant presenting symptoms, with ataxia developing later.
Intellectual disability syndromic and non-syndromic v0.4561 KCND3 Zornitza Stark edited their review of gene: KCND3: Changed rating: GREEN; Changed publications: 32823520
Mendeliome v0.11339 KCND3 Zornitza Stark Phenotypes for gene: KCND3 were changed from Spinocerebellar ataxia 19, MIM# 607346 to Spinocerebellar ataxia 19, MIM# 607346
Mendeliome v0.11338 KCND3 Zornitza Stark Phenotypes for gene: KCND3 were changed from to Spinocerebellar ataxia 19, MIM# 607346
Mendeliome v0.11337 KCND3 Zornitza Stark Publications for gene: KCND3 were set to
Mendeliome v0.11336 KCND3 Zornitza Stark Mode of inheritance for gene: KCND3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11335 KCND3 Zornitza Stark reviewed gene: KCND3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23280837, 23280838, 34361012, 34067185, 33575485, 32823520; Phenotypes: Spinocerebellar ataxia 19, MIM# 607346; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Atrial Fibrillation v0.12 KCNE5 Zornitza Stark Phenotypes for gene: KCNE5 were changed from Atrial fibrillation to Atrial fibrillation
Atrial Fibrillation v0.11 KCNE5 Zornitza Stark Phenotypes for gene: KCNE5 were changed from to Atrial fibrillation
Mendeliome v0.11335 KCNE5 Zornitza Stark Marked gene: KCNE5 as ready
Mendeliome v0.11335 KCNE5 Zornitza Stark Gene: kcne5 has been classified as Red List (Low Evidence).
Atrial Fibrillation v0.10 KCNE5 Zornitza Stark Publications for gene: KCNE5 were set to
Atrial Fibrillation v0.9 KCNE5 Zornitza Stark Mode of inheritance for gene: KCNE5 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Atrial Fibrillation v0.8 KCNE5 Zornitza Stark Classified gene: KCNE5 as Red List (low evidence)
Atrial Fibrillation v0.8 KCNE5 Zornitza Stark Gene: kcne5 has been classified as Red List (Low Evidence).
Atrial Fibrillation v0.7 KCNE5 Zornitza Stark reviewed gene: KCNE5: Rating: RED; Mode of pathogenicity: None; Publications: 18313602, 16054468, 30289750; Phenotypes: Atrial fibrillation; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.11335 KCNE5 Zornitza Stark Phenotypes for gene: KCNE5 were changed from to Atrial fibrillation
Mendeliome v0.11334 KCNE5 Zornitza Stark Publications for gene: KCNE5 were set to
Mendeliome v0.11333 KCNE5 Zornitza Stark Mode of inheritance for gene: KCNE5 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.11332 KCNE5 Zornitza Stark Classified gene: KCNE5 as Red List (low evidence)
Mendeliome v0.11332 KCNE5 Zornitza Stark Gene: kcne5 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1479 KCNJ10 Zornitza Stark Marked gene: KCNJ10 as ready
Genetic Epilepsy v0.1479 KCNJ10 Zornitza Stark Gene: kcnj10 has been classified as Green List (High Evidence).
Mendeliome v0.11331 KCNE5 Zornitza Stark changed review comment from: Associated with Brugada is DISPUTED.

Rare variants in KCNE5 reported in AF cohorts with some supportive functional data.; to: Association with Brugada is DISPUTED.

Rare variants in KCNE5 reported in AF cohorts with some supportive functional data.
Mendeliome v0.11331 KCNE5 Zornitza Stark reviewed gene: KCNE5: Rating: RED; Mode of pathogenicity: None; Publications: 18313602, 16054468, 30289750; Phenotypes: Atrial fibrillation; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic Epilepsy v0.1479 KCNJ10 Zornitza Stark Phenotypes for gene: KCNJ10 were changed from SESAME syndrome, MIM# 612780 to SESAME syndrome, MIM# 612780
Genetic Epilepsy v0.1478 KCNJ10 Zornitza Stark Phenotypes for gene: KCNJ10 were changed from to SESAME syndrome, MIM# 612780
Mendeliome v0.11331 KCNJ10 Zornitza Stark Marked gene: KCNJ10 as ready
Mendeliome v0.11331 KCNJ10 Zornitza Stark Gene: kcnj10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4561 KCNJ10 Zornitza Stark Marked gene: KCNJ10 as ready
Intellectual disability syndromic and non-syndromic v0.4561 KCNJ10 Zornitza Stark Gene: kcnj10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4561 KCNJ10 Zornitza Stark Phenotypes for gene: KCNJ10 were changed from to SESAME syndrome, MIM# 612780
Genetic Epilepsy v0.1477 KCNJ10 Zornitza Stark Publications for gene: KCNJ10 were set to
Genetic Epilepsy v0.1476 KCNJ10 Zornitza Stark Mode of inheritance for gene: KCNJ10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4560 KCNJ10 Zornitza Stark Publications for gene: KCNJ10 were set to
Genetic Epilepsy v0.1475 KCNJ10 Zornitza Stark reviewed gene: KCNJ10: Rating: GREEN; Mode of pathogenicity: None; Publications: 19289823, 19420365, 21849804, 11466414; Phenotypes: SESAME syndrome, MIM# 612780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4559 KCNJ10 Zornitza Stark Mode of inheritance for gene: KCNJ10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11331 KCNJ10 Zornitza Stark Phenotypes for gene: KCNJ10 were changed from to SESAME syndrome, MIM# 612780
Intellectual disability syndromic and non-syndromic v0.4558 KCNJ10 Zornitza Stark reviewed gene: KCNJ10: Rating: GREEN; Mode of pathogenicity: None; Publications: 19289823, 19420365, 21849804, 11466414; Phenotypes: SESAME syndrome, MIM# 612780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11330 KCNJ10 Zornitza Stark Publications for gene: KCNJ10 were set to
Mendeliome v0.11329 KCNJ10 Zornitza Stark Mode of inheritance for gene: KCNJ10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4558 KCNK3 Zornitza Stark Marked gene: KCNK3 as ready
Intellectual disability syndromic and non-syndromic v0.4558 KCNK3 Zornitza Stark Gene: kcnk3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11328 KCNJ10 Zornitza Stark reviewed gene: KCNJ10: Rating: GREEN; Mode of pathogenicity: None; Publications: 19289823, 19420365, 21849804, 11466414; Phenotypes: SESAME syndrome, MIM# 612780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4558 KCNK3 Zornitza Stark Classified gene: KCNK3 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.4558 KCNK3 Zornitza Stark Gene: kcnk3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4558 KCNK3 Zornitza Stark Classified gene: KCNK3 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.4558 KCNK3 Zornitza Stark Gene: kcnk3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11328 KCNK18 Zornitza Stark Marked gene: KCNK18 as ready
Mendeliome v0.11328 KCNK18 Zornitza Stark Gene: kcnk18 has been classified as Green List (High Evidence).
Mendeliome v0.11328 KCNK18 Zornitza Stark Phenotypes for gene: KCNK18 were changed from to {Migraine, with or without aura, susceptibility to, 13}, MIM# 613656
Mendeliome v0.11327 KCNK18 Zornitza Stark Publications for gene: KCNK18 were set to
Mendeliome v0.11326 KCNK18 Zornitza Stark Mode of inheritance for gene: KCNK18 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11325 KCNK18 Zornitza Stark reviewed gene: KCNK18: Rating: GREEN; Mode of pathogenicity: None; Publications: 20871611, 32394190, 30573346, 23904616, 22355750; Phenotypes: {Migraine, with or without aura, susceptibility to, 13}, MIM# 613656; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4557 KCNK3 Zornitza Stark gene: KCNK3 was added
gene: KCNK3 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: KCNK3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNK3 were set to 33057194
Phenotypes for gene: KCNK3 were set to Neurodevelopmental disorder, MONDO:0700092, KCNK3-related
Review for gene: KCNK3 was set to AMBER
Added comment: Established pulmonary hypertension gene.

PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 8 de novo variants (7 missense, 1 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Expert Review
Mendeliome v0.11325 KCNK3 Zornitza Stark Marked gene: KCNK3 as ready
Mendeliome v0.11325 KCNK3 Zornitza Stark Gene: kcnk3 has been classified as Green List (High Evidence).
Mendeliome v0.11325 KCNK3 Zornitza Stark Publications for gene: KCNK3 were set to
Mendeliome v0.11324 KCNK3 Zornitza Stark Phenotypes for gene: KCNK3 were changed from Pulmonary hypertension, primary, 4 MIM#615344 to Pulmonary hypertension, primary, 4 MIM#615344; Neurodevelopmental disorder, MONDO:0700092, KCNK3-related
Aortopathy_Connective Tissue Disorders v1.64 KCNMA1 Zornitza Stark Marked gene: KCNMA1 as ready
Aortopathy_Connective Tissue Disorders v1.64 KCNMA1 Zornitza Stark Gene: kcnma1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v1.64 KCNMA1 Zornitza Stark Classified gene: KCNMA1 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v1.64 KCNMA1 Zornitza Stark Gene: kcnma1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v1.63 KCNMA1 Zornitza Stark gene: KCNMA1 was added
gene: KCNMA1 was added to Aortopathy_Connective Tissue Disorders. Sources: Expert list
Mode of inheritance for gene: KCNMA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNMA1 were set to 31152168
Phenotypes for gene: KCNMA1 were set to Liang-Wang syndrome, MIM# 618729
Review for gene: KCNMA1 was set to GREEN
Added comment: Mono-allelic and bi-allelic variants in this gene are associated with a range of neurological phenotypes.

However, 8 unrelated individuals reported with de novo missense variants and a multiple malformations syndrome, which includes vascular tortuosity/ectasia and aortic aneurysm as features.
Sources: Expert list
Paroxysmal Dyskinesia v0.103 KCNMA1 Zornitza Stark Marked gene: KCNMA1 as ready
Paroxysmal Dyskinesia v0.103 KCNMA1 Zornitza Stark Gene: kcnma1 has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.103 KCNMA1 Zornitza Stark Phenotypes for gene: KCNMA1 were changed from to Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy, MIM# 609446
Paroxysmal Dyskinesia v0.102 KCNMA1 Zornitza Stark Publications for gene: KCNMA1 were set to
Paroxysmal Dyskinesia v0.101 KCNMA1 Zornitza Stark Mode of inheritance for gene: KCNMA1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11323 KCNMA1 Zornitza Stark Marked gene: KCNMA1 as ready
Mendeliome v0.11323 KCNMA1 Zornitza Stark Gene: kcnma1 has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.100 KCNMA1 Zornitza Stark reviewed gene: KCNMA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15937479, 26195193; Phenotypes: Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy, MIM# 609446; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1475 KCNMA1 Zornitza Stark Marked gene: KCNMA1 as ready
Genetic Epilepsy v0.1475 KCNMA1 Zornitza Stark Gene: kcnma1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1475 KCNMA1 Zornitza Stark Phenotypes for gene: KCNMA1 were changed from to Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy, MIM# 609446; Cerebellar atrophy, developmental delay, and seizures, MIM# 617643; Liang-Wang syndrome, MIM# 618729
Genetic Epilepsy v0.1474 KCNMA1 Zornitza Stark Publications for gene: KCNMA1 were set to
Genetic Epilepsy v0.1473 KCNMA1 Zornitza Stark Mode of inheritance for gene: KCNMA1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.1472 KCNMA1 Zornitza Stark reviewed gene: KCNMA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15937479, 26195193, 27567911, 29545233, 31427379, 31152168; Phenotypes: Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy, MIM# 609446, Cerebellar atrophy, developmental delay, and seizures, MIM# 617643, Liang-Wang syndrome, MIM# 618729; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11323 KCNMA1 Zornitza Stark Phenotypes for gene: KCNMA1 were changed from to Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy, MIM# 609446; Cerebellar atrophy, developmental delay, and seizures, MIM# 617643; Liang-Wang syndrome, MIM# 618729
Mendeliome v0.11322 KCNMA1 Zornitza Stark Publications for gene: KCNMA1 were set to
Mendeliome v0.11321 KCNMA1 Zornitza Stark Mode of inheritance for gene: KCNMA1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11320 KCNMA1 Zornitza Stark changed review comment from: Multiple individuals with KCNMA1-related channelopathy described, both mono allelic and bi-allelic disease reported; a variety of neurologic symptoms, including ID; some variants are LoF and some are gain of function, some correlation between mechanism of pathogenicity and phenotype.; to: Multiple individuals with KCNMA1-related channelopathy described, both mono allelic and bi-allelic disease reported; a variety of neurologic symptoms, including ID; some variants are LoF and some are gain of function, some correlation between mechanism of pathogenicity and phenotype.

Liang-Wang syndrome is a polymalformation syndrome with neurological involvement.
Mendeliome v0.11320 KCNMA1 Zornitza Stark reviewed gene: KCNMA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15937479, 26195193, 27567911, 29545233, 31427379, 31152168; Phenotypes: Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy, MIM# 609446, Cerebellar atrophy, developmental delay, and seizures, MIM# 617643, Liang-Wang syndrome, MIM# 618729; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11320 NAT8L Zornitza Stark Marked gene: NAT8L as ready
Mendeliome v0.11320 NAT8L Zornitza Stark Gene: nat8l has been classified as Red List (Low Evidence).
Miscellaneous Metabolic Disorders v1.11 NAT8L Zornitza Stark Marked gene: NAT8L as ready
Miscellaneous Metabolic Disorders v1.11 NAT8L Zornitza Stark Gene: nat8l has been classified as Red List (Low Evidence).
Mendeliome v0.11320 KCNMB1 Zornitza Stark Marked gene: KCNMB1 as ready
Mendeliome v0.11320 KCNMB1 Zornitza Stark Gene: kcnmb1 has been classified as Red List (Low Evidence).
Mendeliome v0.11320 KCNMB1 Zornitza Stark Phenotypes for gene: KCNMB1 were changed from to {Hypertension, diastolic, resistance to} 608622
Miscellaneous Metabolic Disorders v1.11 NAT8L Zornitza Stark Phenotypes for gene: NAT8L were changed from ?N-acetylaspartate deficiency - MIM#614063 to N-acetylaspartate deficiency - MIM#614063
Mendeliome v0.11319 KCNMB1 Zornitza Stark Classified gene: KCNMB1 as Red List (low evidence)
Mendeliome v0.11319 KCNMB1 Zornitza Stark Gene: kcnmb1 has been classified as Red List (Low Evidence).
Mendeliome v0.11318 KCNMB1 Zornitza Stark reviewed gene: KCNMB1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Hypertension, diastolic, resistance to} 608622; Mode of inheritance: None
Mendeliome v0.11318 ECHS1 Zornitza Stark Marked gene: ECHS1 as ready
Mendeliome v0.11318 ECHS1 Zornitza Stark Gene: echs1 has been classified as Green List (High Evidence).
Mendeliome v0.11318 NAT8L Zornitza Stark Phenotypes for gene: NAT8L were changed from to N-acetylaspartate deficiency - MIM#614063
Mendeliome v0.11317 NAT8L Zornitza Stark Publications for gene: NAT8L were set to
Mendeliome v0.11316 NAT8L Zornitza Stark Mode of inheritance for gene: NAT8L was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11315 NAT8L Zornitza Stark Classified gene: NAT8L as Red List (low evidence)
Mendeliome v0.11315 NAT8L Zornitza Stark Gene: nat8l has been classified as Red List (Low Evidence).
Mendeliome v0.11314 NAT8L Zornitza Stark reviewed gene: NAT8L: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: N-acetylaspartate deficiency - MIM#614063; Mode of inheritance: None
Miscellaneous Metabolic Disorders v1.10 NAT8L Zornitza Stark Classified gene: NAT8L as Red List (low evidence)
Miscellaneous Metabolic Disorders v1.10 NAT8L Zornitza Stark Gene: nat8l has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.4556 NAT8L Zornitza Stark Marked gene: NAT8L as ready
Intellectual disability syndromic and non-syndromic v0.4556 NAT8L Zornitza Stark Gene: nat8l has been classified as Red List (Low Evidence).
Miscellaneous Metabolic Disorders v1.9 NAT8L Zornitza Stark reviewed gene: NAT8L: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: N-acetylaspartate deficiency - MIM#614063; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.4556 NAT8L Zornitza Stark Phenotypes for gene: NAT8L were changed from ?N-acetylaspartate deficiency - MIM#614063 to N-acetylaspartate deficiency - MIM#614063
Intellectual disability syndromic and non-syndromic v0.4555 NAT8L Zornitza Stark Classified gene: NAT8L as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.4555 NAT8L Zornitza Stark Gene: nat8l has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.4554 NAT8L Zornitza Stark reviewed gene: NAT8L: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: N-acetylaspartate deficiency - MIM#614063; Mode of inheritance: None
Microcephaly v1.116 NAT8L Zornitza Stark Marked gene: NAT8L as ready
Microcephaly v1.116 NAT8L Zornitza Stark Gene: nat8l has been classified as Red List (Low Evidence).
Microcephaly v1.116 NAT8L Zornitza Stark Phenotypes for gene: NAT8L were changed from N-acetylaspartate deficiency - MIM#614063 to N-acetylaspartate deficiency - MIM#614063
Microcephaly v1.115 NAT8L Zornitza Stark Phenotypes for gene: NAT8L were changed from ?N-acetylaspartate deficiency - MIM#614063 to N-acetylaspartate deficiency - MIM#614063
Genetic Epilepsy v0.1472 NAT8L Zornitza Stark Marked gene: NAT8L as ready
Genetic Epilepsy v0.1472 NAT8L Zornitza Stark Gene: nat8l has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1472 NAT8L Zornitza Stark Phenotypes for gene: NAT8L were changed from ?N-acetylaspartate deficiency - MIM#614063 to N-acetylaspartate deficiency - MIM#614063
Microcephaly v1.114 NAT8L Zornitza Stark Classified gene: NAT8L as Red List (low evidence)
Microcephaly v1.114 NAT8L Zornitza Stark Gene: nat8l has been classified as Red List (Low Evidence).
Microcephaly v1.113 NAT8L Zornitza Stark reviewed gene: NAT8L: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: N-acetylaspartate deficiency - MIM#614063; Mode of inheritance: None
Genetic Epilepsy v0.1471 NAT8L Zornitza Stark Classified gene: NAT8L as Red List (low evidence)
Genetic Epilepsy v0.1471 NAT8L Zornitza Stark Gene: nat8l has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1470 NAT8L Zornitza Stark reviewed gene: NAT8L: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: N-acetylaspartate deficiency - MIM#614063; Mode of inheritance: None
Mendeliome v0.11314 NAT2 Zornitza Stark Marked gene: NAT2 as ready
Mendeliome v0.11314 NAT2 Zornitza Stark Gene: nat2 has been classified as Red List (Low Evidence).
Mendeliome v0.11314 NAT2 Zornitza Stark Phenotypes for gene: NAT2 were changed from to [Acetylation, slow] - MIM#243400
Mendeliome v0.11313 NAT2 Zornitza Stark Publications for gene: NAT2 were set to
Mendeliome v0.11312 NAT2 Zornitza Stark Mode of inheritance for gene: NAT2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11311 NAT2 Zornitza Stark Classified gene: NAT2 as Red List (low evidence)
Mendeliome v0.11311 NAT2 Zornitza Stark Gene: nat2 has been classified as Red List (Low Evidence).
Mendeliome v0.11310 EDA Bryony Thompson Marked gene: EDA as ready
Mendeliome v0.11310 EDA Bryony Thompson Gene: eda has been classified as Green List (High Evidence).
Mendeliome v0.11310 EDA Bryony Thompson Phenotypes for gene: EDA were changed from to Ectodermal dysplasia 1, hypohidrotic, X-linked MIM#305100; Tooth agenesis, selective, X-linked 1 MIM#313500
Mendeliome v0.11309 EDA Bryony Thompson Publications for gene: EDA were set to
Mendeliome v0.11308 EDA Bryony Thompson Mode of inheritance for gene: EDA was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.11307 EDA Bryony Thompson reviewed gene: EDA: Rating: GREEN; Mode of pathogenicity: None; Publications: 27144394, 8696334, 9507389, 9683615, 18657636; Phenotypes: Ectodermal dysplasia 1, hypohidrotic, X-linked MIM#305100, Tooth agenesis, selective, X-linked 1 MIM#313500; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.11307 ECHS1 Bryony Thompson Phenotypes for gene: ECHS1 were changed from to Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, MIM# 616277; Leigh syndrome MONDO:0009723; cerebral palsy MONDO:0006497; paroxysmal dystonia MONDO:0016058
Mendeliome v0.11306 ECHS1 Bryony Thompson Publications for gene: ECHS1 were set to
Mitochondrial disease v0.711 ECHS1 Bryony Thompson Marked gene: ECHS1 as ready
Mitochondrial disease v0.711 ECHS1 Bryony Thompson Gene: echs1 has been classified as Green List (High Evidence).
Mendeliome v0.11305 ECHS1 Bryony Thompson Mode of inheritance for gene: ECHS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11304 ECHS1 Bryony Thompson reviewed gene: ECHS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33528536, 34364746, 32858208, 31399326, 25125611, 25393721, 32677093; Phenotypes: Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, MIM# 616277, Leigh syndrome MONDO:0009723, cerebral palsy MONDO:0006497, paroxysmal dystonia MONDO:0016058; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mitochondrial disease v0.711 ECHS1 Bryony Thompson Phenotypes for gene: ECHS1 were changed from to Leigh syndrome MONDO:0009723
Mitochondrial disease v0.710 ECHS1 Bryony Thompson Publications for gene: ECHS1 were set to
Mitochondrial disease v0.709 ECHS1 Bryony Thompson Mode of inheritance for gene: ECHS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.708 ECHS1 Bryony Thompson reviewed gene: ECHS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26000322, 25393721, 25125611, 28409271, 29575569, 28755360, 26099313; Phenotypes: Leigh syndrome MONDO:0009723; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.4554 ARHGAP35 Ain Roesley Phenotypes for gene: ARHGAP35 were changed from neurodevelopmental disorder, ARHGAP35-related MONDO#0700092 to neurodevelopmental disorder, ARHGAP35-related MONDO#0700092
Intellectual disability syndromic and non-syndromic v0.4553 ARHGAP35 Ain Roesley Phenotypes for gene: ARHGAP35 were changed from neurodevelopmental disorder, ARHGAP35-related MONDO#0700092 to neurodevelopmental disorder, ARHGAP35-related MONDO#0700092
Intellectual disability syndromic and non-syndromic v0.4552 ARHGAP35 Ain Roesley Phenotypes for gene: ARHGAP35 were changed from neurodevelopmental disorder, ARHGAP35-related MONDO#0700092 to neurodevelopmental disorder, ARHGAP35-related MONDO#0700092
Intellectual disability syndromic and non-syndromic v0.4552 ARHGAP35 Ain Roesley Phenotypes for gene: ARHGAP35 were changed from Developmental disorder to neurodevelopmental disorder, ARHGAP35-related MONDO#0700092
Intellectual disability syndromic and non-syndromic v0.4551 ARHGAP35 Ain Roesley Classified gene: ARHGAP35 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4551 ARHGAP35 Ain Roesley Gene: arhgap35 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4551 ARHGAP35 Ain Roesley Classified gene: ARHGAP35 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4551 ARHGAP35 Ain Roesley Gene: arhgap35 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4550 ARHGAP35 Ain Roesley reviewed gene: ARHGAP35: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder, ARHGAP35-related MONDO#0700092; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.11304 ARHGAP35 Ain Roesley Phenotypes for gene: ARHGAP35 were changed from Developmental disorder to neurodevelopmental disorder, ARHGAP35-related MONDO#0700092
Mendeliome v0.11303 ARHGAP35 Ain Roesley Classified gene: ARHGAP35 as Green List (high evidence)
Mendeliome v0.11303 ARHGAP35 Ain Roesley Gene: arhgap35 has been classified as Green List (High Evidence).
Mendeliome v0.11302 ARHGAP35 Ain Roesley Classified gene: ARHGAP35 as Green List (high evidence)
Mendeliome v0.11302 ARHGAP35 Ain Roesley Gene: arhgap35 has been classified as Green List (High Evidence).
Mendeliome v0.11301 ARHGAP35 Ain Roesley reviewed gene: ARHGAP35: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder, ARHGAP35-related MONDO#0700092; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.11301 KCNV2 Zornitza Stark Marked gene: KCNV2 as ready
Mendeliome v0.11301 KCNV2 Zornitza Stark Gene: kcnv2 has been classified as Green List (High Evidence).
Mendeliome v0.11301 KCNV2 Zornitza Stark Phenotypes for gene: KCNV2 were changed from to Retinal cone dystrophy 3B, MIM# 610356
Mendeliome v0.11300 KCNV2 Zornitza Stark Publications for gene: KCNV2 were set to
Cone-rod Dystrophy v0.32 KCNV2 Zornitza Stark Marked gene: KCNV2 as ready
Cone-rod Dystrophy v0.32 KCNV2 Zornitza Stark Gene: kcnv2 has been classified as Green List (High Evidence).
Cone-rod Dystrophy v0.32 KCNV2 Zornitza Stark Publications for gene: KCNV2 were set to 30679166
Mendeliome v0.11299 KCNV2 Zornitza Stark Mode of inheritance for gene: KCNV2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cone-rod Dystrophy v0.31 KCNV2 Zornitza Stark reviewed gene: KCNV2: Rating: GREEN; Mode of pathogenicity: None; Publications: 16909397, 18235024, 21882291; Phenotypes: Retinal cone dystrophy 3B, MIM# 610356; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11298 KCNV2 Zornitza Stark reviewed gene: KCNV2: Rating: GREEN; Mode of pathogenicity: None; Publications: 16909397, 18235024, 21882291; Phenotypes: Retinal cone dystrophy 3B, MIM# 610356; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11298 KHDC3L Zornitza Stark Marked gene: KHDC3L as ready
Mendeliome v0.11298 KHDC3L Zornitza Stark Gene: khdc3l has been classified as Green List (High Evidence).
Mendeliome v0.11298 KHDC3L Zornitza Stark Phenotypes for gene: KHDC3L were changed from to Hydatiform mold recurrent 2, MIM#614293
Mendeliome v0.11297 KHDC3L Zornitza Stark Publications for gene: KHDC3L were set to
Mendeliome v0.11296 KHDC3L Zornitza Stark Mode of inheritance for gene: KHDC3L was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11295 KHDC3L Zornitza Stark reviewed gene: KHDC3L: Rating: GREEN; Mode of pathogenicity: None; Publications: 23232697, 31847873, 23125094, 21885028; Phenotypes: Hydatiform mold recurrent 2 MIM#614293; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4550 KIAA1109 Zornitza Stark Phenotypes for gene: KIAA1109 were changed from Alkuraya-Kucinskas syndrome, MIM# 617822 to Alkuraya-Kucinskas syndrome, MIM# 617822
Intellectual disability syndromic and non-syndromic v0.4550 KIAA1109 Zornitza Stark Marked gene: KIAA1109 as ready
Intellectual disability syndromic and non-syndromic v0.4550 KIAA1109 Zornitza Stark Gene: kiaa1109 has been classified as Green List (High Evidence).
Arthrogryposis v0.328 KIAA1109 Zornitza Stark Marked gene: KIAA1109 as ready
Arthrogryposis v0.328 KIAA1109 Zornitza Stark Gene: kiaa1109 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4550 KIAA1109 Zornitza Stark Phenotypes for gene: KIAA1109 were changed from Alkuraya-Kucinskas syndrome, MIM# 617822 to Alkuraya-Kucinskas syndrome, MIM# 617822
Arthrogryposis v0.328 KIAA1109 Zornitza Stark Mode of inheritance for gene: KIAA1109 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.327 KIAA1109 Zornitza Stark Mode of inheritance for gene: KIAA1109 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4550 KIAA1109 Zornitza Stark Phenotypes for gene: KIAA1109 were changed from to Alkuraya-Kucinskas syndrome, MIM# 617822
Arthrogryposis v0.327 KIAA1109 Zornitza Stark Publications for gene: KIAA1109 were set to
Intellectual disability syndromic and non-syndromic v0.4549 KIAA1109 Zornitza Stark Publications for gene: KIAA1109 were set to
Intellectual disability syndromic and non-syndromic v0.4548 KIAA1109 Zornitza Stark Mode of inheritance for gene: KIAA1109 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.326 KIAA1109 Zornitza Stark Phenotypes for gene: KIAA1109 were changed from to Alkuraya-Kucinskas syndrome, MIM# 617822
Intellectual disability syndromic and non-syndromic v0.4547 KIAA1109 Zornitza Stark reviewed gene: KIAA1109: Rating: GREEN; Mode of pathogenicity: None; Publications: 29290337, 30906834; Phenotypes: Alkuraya-Kucinskas syndrome, MIM# 617822; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.325 KIAA1109 Zornitza Stark reviewed gene: KIAA1109: Rating: GREEN; Mode of pathogenicity: None; Publications: 29290337, 30906834; Phenotypes: Alkuraya-Kucinskas syndrome, MIM# 617822; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11295 KIAA1109 Zornitza Stark changed review comment from: ALKKUCS is an autosomal recessive severe neurodevelopmental disorder characterized by arthrogryposis, brain abnormalities associated with cerebral parenchymal underdevelopment, and global developmental delay. Most affected individuals die in utero or soon after birth. Additional abnormalities may include hypotonia, dysmorphic facial features, and involvement of other organ systems, such as cardiac or renal. The few patients who survive have variable intellectual disability and may have seizures.; to: ALKKUCS is an autosomal recessive severe neurodevelopmental disorder characterized by arthrogryposis, brain abnormalities associated with cerebral parenchymal underdevelopment, and global developmental delay. Most affected individuals die in utero or soon after birth. Additional abnormalities may include hypotonia, dysmorphic facial features, and involvement of other organ systems, such as cardiac or renal. The few patients who survive have variable intellectual disability and may have seizures.

More than 10 families reported.
Mendeliome v0.11295 KIAA1109 Zornitza Stark Marked gene: KIAA1109 as ready
Mendeliome v0.11295 KIAA1109 Zornitza Stark Gene: kiaa1109 has been classified as Green List (High Evidence).
Mendeliome v0.11295 KIAA1109 Zornitza Stark Phenotypes for gene: KIAA1109 were changed from to Alkuraya-Kucinskas syndrome, MIM# 617822
Mendeliome v0.11294 KIAA1109 Zornitza Stark Publications for gene: KIAA1109 were set to
Mendeliome v0.11293 KIAA1109 Zornitza Stark Mode of inheritance for gene: KIAA1109 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11292 KIAA1109 Zornitza Stark reviewed gene: KIAA1109: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Alkuraya-Kucinskas syndrome, MIM# 617822; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11292 KIF1A Zornitza Stark Marked gene: KIF1A as ready
Mendeliome v0.11292 KIF1A Zornitza Stark Gene: kif1a has been classified as Green List (High Evidence).
Mendeliome v0.11292 KIF1A Zornitza Stark Phenotypes for gene: KIF1A were changed from to Neuropathy, hereditary sensory, type IIC, MIM# 614213; NESCAV syndrome, MIM# 614255; Spastic paraplegia 30, MIM# 610357
Mendeliome v0.11291 KIF1A Zornitza Stark Publications for gene: KIF1A were set to
Mendeliome v0.11290 KIF1A Zornitza Stark Mode of inheritance for gene: KIF1A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11289 KIF1A Zornitza Stark edited their review of gene: KIF1A: Changed phenotypes: Neuropathy, hereditary sensory, type IIC, MIM# 614213, NESCAV syndrome, MIM# 614255, Spastic paraplegia 30, MIM# 610357; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11289 KIF5A Zornitza Stark Marked gene: KIF5A as ready
Mendeliome v0.11289 KIF5A Zornitza Stark Gene: kif5a has been classified as Green List (High Evidence).
Mendeliome v0.11289 KIF5A Zornitza Stark Phenotypes for gene: KIF5A were changed from to Neuropathy; Spastic paraplegia 10, autosomal dominant, MIM# 604187; Myoclonus, intractable, neonatal, MIM# 617235
Mendeliome v0.11288 KIF5A Zornitza Stark Publications for gene: KIF5A were set to
Mendeliome v0.11287 KIF5A Zornitza Stark Mode of inheritance for gene: KIF5A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11286 KIF5A Zornitza Stark edited their review of gene: KIF5A: Added comment: Neonatal intractable myoclonus is a severe neurologic disorder characterized by the onset of intractable myoclonic seizures soon after birth. Affected infants have intermittent apnea, abnormal eye movements, pallor of the optic nerve, and lack of developmental progress. Brain imaging shows a progressive leukoencephalopathy. At least 3 unrelated individuals with de novo LoF variants.

SPG10/CMT: variants are generally in the motor domain.; Changed publications: 30057544, 29892902, 28902413, 26403765, 25695920, 25008398, 27463701, 27414745; Changed phenotypes: Neuropathy, Spastic paraplegia 10, autosomal dominant, MIM# 604187, Myoclonus, intractable, neonatal, MIM# 617235
Mendeliome v0.11286 KIT Zornitza Stark Marked gene: KIT as ready
Mendeliome v0.11286 KIT Zornitza Stark Gene: kit has been classified as Green List (High Evidence).
Mendeliome v0.11286 KIT Zornitza Stark Phenotypes for gene: KIT were changed from to Piebaldism, MIM# 172800; Gastrointestinal stromal tumor, familial, MIM# 606764; Mastocytosis, cutaneous, MIM# 154800
Mendeliome v0.11285 KIT Zornitza Stark Mode of inheritance for gene: KIT was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11284 KIT Zornitza Stark reviewed gene: KIT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Piebaldism, MIM# 172800, Gastrointestinal stromal tumor, familial, MIM# 606764, Mastocytosis, cutaneous, MIM# 154800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinitis pigmentosa v0.109 KIZ Zornitza Stark Marked gene: KIZ as ready
Retinitis pigmentosa v0.109 KIZ Zornitza Stark Gene: kiz has been classified as Green List (High Evidence).
Retinitis pigmentosa v0.109 KIZ Zornitza Stark Phenotypes for gene: KIZ were changed from Retinitis pigmentosa 69 to Retinitis pigmentosa 69, MIM# 615780
Retinitis pigmentosa v0.108 KIZ Zornitza Stark Publications for gene: KIZ were set to
Retinitis pigmentosa v0.107 KIZ Zornitza Stark reviewed gene: KIZ: Rating: GREEN; Mode of pathogenicity: None; Publications: 24680887, 31556760, 29057815; Phenotypes: Retinitis pigmentosa 69, MIM# 615780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11284 KIZ Zornitza Stark Marked gene: KIZ as ready
Mendeliome v0.11284 KIZ Zornitza Stark Gene: kiz has been classified as Green List (High Evidence).
Mendeliome v0.11284 KIZ Zornitza Stark Phenotypes for gene: KIZ were changed from to Retinitis pigmentosa 69, MIM# 615780
Mendeliome v0.11283 KIZ Zornitza Stark Publications for gene: KIZ were set to
Mendeliome v0.11282 KIZ Zornitza Stark Mode of inheritance for gene: KIZ was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11281 KIZ Zornitza Stark reviewed gene: KIZ: Rating: GREEN; Mode of pathogenicity: None; Publications: 24680887, 31556760, 29057815; Phenotypes: Retinitis pigmentosa 69, MIM# 615780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11281 KLF11 Zornitza Stark Marked gene: KLF11 as ready
Mendeliome v0.11281 KLF11 Zornitza Stark Gene: klf11 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11281 KLF11 Zornitza Stark Phenotypes for gene: KLF11 were changed from to Maturity-onset diabetes of the young, type VII MIM#610508
Mendeliome v0.11280 KLF11 Zornitza Stark Publications for gene: KLF11 were set to
Mendeliome v0.11279 KLF11 Zornitza Stark Mode of inheritance for gene: KLF11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11278 KLF11 Zornitza Stark Classified gene: KLF11 as Amber List (moderate evidence)
Mendeliome v0.11278 KLF11 Zornitza Stark Gene: klf11 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11277 KLF6 Zornitza Stark Marked gene: KLF6 as ready
Mendeliome v0.11277 KLF6 Zornitza Stark Gene: klf6 has been classified as Red List (Low Evidence).
Mendeliome v0.11277 KLF6 Zornitza Stark Classified gene: KLF6 as Red List (low evidence)
Mendeliome v0.11277 KLF6 Zornitza Stark Gene: klf6 has been classified as Red List (Low Evidence).
Mendeliome v0.11276 KLF6 Zornitza Stark reviewed gene: KLF6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.11276 KLHDC8B Zornitza Stark Marked gene: KLHDC8B as ready
Mendeliome v0.11276 KLHDC8B Zornitza Stark Gene: klhdc8b has been classified as Red List (Low Evidence).
Mendeliome v0.11276 KLHDC8B Zornitza Stark Phenotypes for gene: KLHDC8B were changed from to {Hodgkin lymphoma, susceptibility to} 236000
Mendeliome v0.11275 KLHDC8B Zornitza Stark Classified gene: KLHDC8B as Red List (low evidence)
Mendeliome v0.11275 KLHDC8B Zornitza Stark Gene: klhdc8b has been classified as Red List (Low Evidence).
Mendeliome v0.11274 KLHDC8B Zornitza Stark reviewed gene: KLHDC8B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Hodgkin lymphoma, susceptibility to} 236000; Mode of inheritance: None
Mendeliome v0.11274 KLHL10 Zornitza Stark Marked gene: KLHL10 as ready
Mendeliome v0.11274 KLHL10 Zornitza Stark Gene: klhl10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11274 KLHL10 Zornitza Stark Phenotypes for gene: KLHL10 were changed from to Spermatogenic failure 11, MIM# 615081
Mendeliome v0.11273 KLHL10 Zornitza Stark Publications for gene: KLHL10 were set to
Mendeliome v0.11272 KLHL10 Zornitza Stark Mode of inheritance for gene: KLHL10 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11271 KLHL10 Zornitza Stark Classified gene: KLHL10 as Amber List (moderate evidence)
Mendeliome v0.11271 KLHL10 Zornitza Stark Gene: klhl10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11270 KLHL10 Zornitza Stark reviewed gene: KLHL10: Rating: AMBER; Mode of pathogenicity: None; Publications: 17047026, 15136734, 31479588; Phenotypes: Spermatogenic failure 11, MIM# 615081; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4547 FBXO28 Zornitza Stark Phenotypes for gene: FBXO28 were changed from Developmental and epileptic encephalopathy to Developmental and epileptic encephalopathy 100, MIM# 619777
Intellectual disability syndromic and non-syndromic v0.4546 FBXO28 Zornitza Stark edited their review of gene: FBXO28: Changed phenotypes: Developmental and epileptic encephalopathy 100, MIM# 619777
Genetic Epilepsy v0.1470 FBXO28 Zornitza Stark Phenotypes for gene: FBXO28 were changed from Developmental and epileptic encephalopathy to Developmental and epileptic encephalopathy 100, MIM# 619777
Genetic Epilepsy v0.1469 FBXO28 Zornitza Stark edited their review of gene: FBXO28: Changed phenotypes: Developmental and epileptic encephalopathy 100, MIM# 619777
Mendeliome v0.11270 FBXO28 Zornitza Stark Phenotypes for gene: FBXO28 were changed from Developmental and epileptic encephalopathy to Developmental and epileptic encephalopathy 100, MIM# 619777
Mendeliome v0.11269 FBXO28 Zornitza Stark edited their review of gene: FBXO28: Changed phenotypes: Developmental and epileptic encephalopathy 100, MIM# 619777
Renal Macrocystic Disease v0.42 DZIP1L Yu Leng Phua Deleted their review
Renal Macrocystic Disease v0.42 DZIP1L Yu Leng Phua Deleted their comment
Aortopathy_Connective Tissue Disorders v1.62 TLN1 Bryony Thompson Marked gene: TLN1 as ready
Aortopathy_Connective Tissue Disorders v1.62 TLN1 Bryony Thompson Gene: tln1 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v1.62 TLN1 Bryony Thompson Classified gene: TLN1 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v1.62 TLN1 Bryony Thompson Gene: tln1 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v1.61 TLN1 Bryony Thompson gene: TLN1 was added
gene: TLN1 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: TLN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TLN1 were set to 30888838
Phenotypes for gene: TLN1 were set to idiopathic spontaneous coronary artery dissection MONDO:0007385
Review for gene: TLN1 was set to AMBER
Added comment: 10 unique rare heterozygous missense variants in 11 individuals were identified in a 2 generation SCAD family and 56 unrelated individuals with sporadic SCAD. All variants had a MAF of less than 0.06% and occurred within highly conserved β-integrin, F-actin, or vinculin binding domains. Incomplete penetrance was evident in the familial case and five individuals with sporadic SCAD from whom parental DNA was available. No functional assays were conducted.
Sources: Literature
Renal Macrocystic Disease v0.42 DZIP1L Yu Leng Phua reviewed gene: DZIP1L: Rating: GREEN; Mode of pathogenicity: None; Publications: 35211789; Phenotypes: Polycystic kidney disease 5, MIM#617610; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11269 TLN1 Bryony Thompson Marked gene: TLN1 as ready
Mendeliome v0.11269 TLN1 Bryony Thompson Gene: tln1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11269 TLN1 Bryony Thompson Classified gene: TLN1 as Amber List (moderate evidence)
Mendeliome v0.11269 TLN1 Bryony Thompson Gene: tln1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11268 TLN1 Bryony Thompson gene: TLN1 was added
gene: TLN1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TLN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TLN1 were set to 30888838
Phenotypes for gene: TLN1 were set to idiopathic spontaneous coronary artery dissection MONDO:0007385
Review for gene: TLN1 was set to AMBER
Added comment: 10 unique rare heterozygous missense variants in 11 individuals were identified in a 2 generation SCAD family and 56 unrelated individuals with sporadic SCAD. All variants had a MAF of less than 0.06% and occurred within highly conserved β-integrin, F-actin, or vinculin binding domains. Incomplete penetrance was evident in the familial case and five individuals with sporadic SCAD from whom parental DNA was available. No functional assays were conducted.
Sources: Literature
Mendeliome v0.11267 NAT8L Krithika Murali reviewed gene: NAT8L: Rating: AMBER; Mode of pathogenicity: None; Publications: 11310630, 19807691, 32275776; Phenotypes: ?N-acetylaspartate deficiency - MIM#614063; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Miscellaneous Metabolic Disorders v1.9 NAT8L Krithika Murali gene: NAT8L was added
gene: NAT8L was added to Miscellaneous Metabolic Disorders. Sources: Literature
Mode of inheritance for gene: NAT8L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAT8L were set to 11310630; 19807691; 32275776
Phenotypes for gene: NAT8L were set to ?N-acetylaspartate deficiency - MIM#614063
Review for gene: NAT8L was set to AMBER
Added comment: Absence of brain N-acetylaspartate, has been described in only one patient, with truncal ataxia, marked developmental delay, seizures and secondary microcephaly (first described by - PMID: 11310630 Martin et al 2001). PMID: 19807691 - Wiame et al 2009 identified in this patient a homozygous 19 bp NAT8L gene deletion, resulting in a change in reading frame and the absence of production of a functional protein. The affected individual is adopted and testing of the biological parents was not possible. The authors provide supportive functional studies.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4546 NAT8L Krithika Murali gene: NAT8L was added
gene: NAT8L was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: NAT8L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAT8L were set to 11310630; 19807691; 32275776
Phenotypes for gene: NAT8L were set to ?N-acetylaspartate deficiency - MIM#614063
Review for gene: NAT8L was set to AMBER
Added comment: Absence of brain N-acetylaspartate, has been described in only one patient, with truncal ataxia, marked developmental delay, seizures and secondary microcephaly (first described by - PMID: 11310630 Martin et al 2001). PMID: 19807691 - Wiame et al 2009 identified in this patient a homozygous 19 bp NAT8L gene deletion, resulting in a change in reading frame and the absence of production of a functional protein. The affected individual is adopted and testing of the biological parents was not possible. The authors provide supportive functional studies.
Sources: Literature
Microcephaly v1.113 NAT8L Krithika Murali gene: NAT8L was added
gene: NAT8L was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: NAT8L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAT8L were set to 11310630; 19807691; 32275776
Phenotypes for gene: NAT8L were set to ?N-acetylaspartate deficiency - MIM#614063
Review for gene: NAT8L was set to AMBER
Added comment: Absence of brain N-acetylaspartate, has been described in only one patient, with truncal ataxia, marked developmental delay, seizures and secondary microcephaly (first described by - PMID: 11310630 Martin et al 2001). PMID: 19807691 - Wiame et al 2009 identified in this patient a homozygous 19 bp NAT8L gene deletion, resulting in a change in reading frame and the absence of production of a functional protein. The affected individual is adopted and testing of the biological parents was not possible. The authors provide supportive functional studies.
Sources: Literature
Genetic Epilepsy v0.1469 NAT8L Krithika Murali gene: NAT8L was added
gene: NAT8L was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: NAT8L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAT8L were set to 11310630; 19807691; 32275776
Phenotypes for gene: NAT8L were set to ?N-acetylaspartate deficiency - MIM#614063
Review for gene: NAT8L was set to AMBER
Added comment: Absence of brain N-acetylaspartate, has been described in only one patient, with truncal ataxia, marked developmental delay, seizures and secondary microcephaly (first described by - PMID: 11310630 Martin et al 2001). PMID: 19807691 - Wiame et al 2009 identified in this patient a homozygous 19 bp NAT8L gene deletion, resulting in a change in reading frame and the absence of production of a functional protein. The affected individual is adopted and testing of the biological parents was not possible. The authors provide supportive functional studies.
Sources: Literature
Mendeliome v0.11267 KLK1 Zornitza Stark Marked gene: KLK1 as ready
Mendeliome v0.11267 KLK1 Zornitza Stark Gene: klk1 has been classified as Red List (Low Evidence).
Mendeliome v0.11267 KLK1 Zornitza Stark Phenotypes for gene: KLK1 were changed from to [Kallikrein, decreased urinary activity of] 615953
Mendeliome v0.11266 KLK1 Zornitza Stark Classified gene: KLK1 as Red List (low evidence)
Mendeliome v0.11266 KLK1 Zornitza Stark Gene: klk1 has been classified as Red List (Low Evidence).
Mendeliome v0.11265 KLK1 Zornitza Stark reviewed gene: KLK1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: [Kallikrein, decreased urinary activity of] 615953; Mode of inheritance: None
Bleeding and Platelet Disorders v1.6 KLKB1 Zornitza Stark Marked gene: KLKB1 as ready
Bleeding and Platelet Disorders v1.6 KLKB1 Zornitza Stark Gene: klkb1 has been classified as Amber List (Moderate Evidence).
Bleeding and Platelet Disorders v1.6 KLKB1 Zornitza Stark Classified gene: KLKB1 as Amber List (moderate evidence)
Bleeding and Platelet Disorders v1.6 KLKB1 Zornitza Stark Gene: klkb1 has been classified as Amber List (Moderate Evidence).
Bleeding and Platelet Disorders v1.5 KLKB1 Zornitza Stark gene: KLKB1 was added
gene: KLKB1 was added to Bleeding and Platelet Disorders. Sources: Expert Review
Mode of inheritance for gene: KLKB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KLKB1 were set to 15461630; 33073460
Phenotypes for gene: KLKB1 were set to Fletcher factor (prekallikrein) deficiency, MIM# 612423
Review for gene: KLKB1 was set to AMBER
Added comment: Prolonged aPTT, but asymptomatic, hence some variants have a high gnomad frequency.
Sources: Expert Review
Mendeliome v0.11265 KLKB1 Zornitza Stark Marked gene: KLKB1 as ready
Mendeliome v0.11265 KLKB1 Zornitza Stark Gene: klkb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11265 KLKB1 Zornitza Stark Phenotypes for gene: KLKB1 were changed from to Fletcher factor (prekallikrein) deficiency, MIM# 612423
Mendeliome v0.11264 KLKB1 Zornitza Stark Publications for gene: KLKB1 were set to
Mendeliome v0.11263 KLKB1 Zornitza Stark Mode of inheritance for gene: KLKB1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11262 KLKB1 Zornitza Stark Classified gene: KLKB1 as Amber List (moderate evidence)
Mendeliome v0.11262 KLKB1 Zornitza Stark Gene: klkb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11261 KLKB1 Zornitza Stark reviewed gene: KLKB1: Rating: AMBER; Mode of pathogenicity: None; Publications: 15461630, 33073460; Phenotypes: Fletcher factor (prekallikrein) deficiency, MIM# 612423; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11261 KRT1 Zornitza Stark Marked gene: KRT1 as ready
Mendeliome v0.11261 KRT1 Zornitza Stark Gene: krt1 has been classified as Green List (High Evidence).
Mendeliome v0.11261 KRT1 Zornitza Stark Phenotypes for gene: KRT1 were changed from to Epidermolytic hyperkeratosis, MIM#113800; Ichthyosis, cyclic, with epidermolytic hyperkeratosis, MIM# 607602; Ichthyosis histrix, Curth-Macklin type, MIM# 146590; Palmoplantar keratoderma, epidermolytic, MIM# 144200; Palmoplantar keratoderma, nonepidermolytic, MIM# 600962
Mendeliome v0.11260 KRT1 Zornitza Stark Publications for gene: KRT1 were set to
Mendeliome v0.11259 KRT1 Zornitza Stark Mode of inheritance for gene: KRT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11258 KRT1 Zornitza Stark reviewed gene: KRT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 7511022, 21271994, 11286630; Phenotypes: Epidermolytic hyperkeratosis, MIM#113800, Ichthyosis, cyclic, with epidermolytic hyperkeratosis, MIM# 607602, Ichthyosis histrix, Curth-Macklin type, MIM# 146590, Palmoplantar keratoderma, epidermolytic, MIM# 144200, Palmoplantar keratoderma, nonepidermolytic, MIM# 600962; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11258 KRT12 Zornitza Stark Marked gene: KRT12 as ready
Mendeliome v0.11258 KRT12 Zornitza Stark Gene: krt12 has been classified as Green List (High Evidence).
Mendeliome v0.11258 KRT12 Zornitza Stark Phenotypes for gene: KRT12 were changed from to Meesmann corneal dystrophy 1, MIM# 122100
Mendeliome v0.11257 KRT12 Zornitza Stark Publications for gene: KRT12 were set to
Mendeliome v0.11256 KRT12 Zornitza Stark Mode of inheritance for gene: KRT12 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11255 KRT12 Zornitza Stark reviewed gene: KRT12: Rating: GREEN; Mode of pathogenicity: None; Publications: 9171831, 22174841; Phenotypes: Meesmann corneal dystrophy 1, MIM# 122100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11255 NAT2 Krithika Murali reviewed gene: NAT2: Rating: RED; Mode of pathogenicity: None; Publications: 22409928, 33932406; Phenotypes: [Acetylation, slow] - MIM#243400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11255 TSR1 Bryony Thompson Marked gene: TSR1 as ready
Mendeliome v0.11255 TSR1 Bryony Thompson Gene: tsr1 has been classified as Red List (Low Evidence).
Mendeliome v0.11255 TSR1 Bryony Thompson gene: TSR1 was added
gene: TSR1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TSR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TSR1 were set to 31296288; 31296287
Phenotypes for gene: TSR1 were set to idiopathic spontaneous coronary artery dissection MONDO:0007385
Review for gene: TSR1 was set to RED
Added comment: A single case-control study with 85 SCAD cases and 296 non-SCAD controls from the Chinese Han population that underwent exome sequencing. TSR1 was the top hit in association analyses (p < 5.41 × 10-5 in both the optimal sequence kernel association and mixed effects score tests), with 5 variants identified in 8 SCAD cases.
Sources: Literature
Mendeliome v0.11254 TMEM151A Bryony Thompson Marked gene: TMEM151A as ready
Mendeliome v0.11254 TMEM151A Bryony Thompson Gene: tmem151a has been classified as Green List (High Evidence).
Mendeliome v0.11254 TMEM151A Bryony Thompson Classified gene: TMEM151A as Green List (high evidence)
Mendeliome v0.11254 TMEM151A Bryony Thompson Gene: tmem151a has been classified as Green List (High Evidence).
Mendeliome v0.11253 TMEM151A Bryony Thompson gene: TMEM151A was added
gene: TMEM151A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TMEM151A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TMEM151A were set to 34820915; 34518509
Phenotypes for gene: TMEM151A were set to episodic kinesigenic dyskinesia MONDO:0044202
Review for gene: TMEM151A was set to GREEN
Added comment: PMID: 34820915 - 24 heterozygous TMEM151A variants detected in 29 PRRT2-negative patients from 25 families
PMID: 34518509 - TMEM151A variants identified in 3 AD families and 8 isolated PKD patients with incomplete penetrance identified in 3 of the isolated cases. Also, supporting mouse model and in vitro functional assays suggesting loss of function as the mechanism of disease.
Sources: Literature
Paroxysmal Dyskinesia v0.100 TMEM151A Bryony Thompson Phenotypes for gene: TMEM151A were changed from Paroxysmal Kinesigenic Dyskinesia to Paroxysmal Kinesigenic Dyskinesia; episodic kinesigenic dyskinesia MONDO:0044202
Paroxysmal Dyskinesia v0.99 TMEM151A Bryony Thompson Classified gene: TMEM151A as Green List (high evidence)
Paroxysmal Dyskinesia v0.99 TMEM151A Bryony Thompson Added comment: Comment on list classification: PMID: 34820915 - 24 heterozygous TMEM151A variants detected in 29 PRRT2-negative patients from 25 families
PMID: 34518509 - TMEM151A variants identified in 3 AD families and 8 isolated PKD patients with incomplete penetrance identified in 3 of the isolated cases. Also, supporting mouse model and in vitro functional assays suggesting loss of function as the mechanism of disease.
Paroxysmal Dyskinesia v0.99 TMEM151A Bryony Thompson Gene: tmem151a has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v1.24 ATP6AP2 Bryony Thompson Mode of inheritance for gene: ATP6AP2 was changed from BIALLELIC, autosomal or pseudoautosomal to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Paroxysmal Dyskinesia v0.98 TMEM151A Shekeeb Mohammad gene: TMEM151A was added
gene: TMEM151A was added to Paroxysmal Dyskinesia. Sources: Literature
Mode of inheritance for gene: TMEM151A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TMEM151A were set to 34820915; 34518509
Phenotypes for gene: TMEM151A were set to Paroxysmal Kinesigenic Dyskinesia
Review for gene: TMEM151A was set to GREEN
Added comment: Sources: Literature
Mendeliome v0.11252 KRT13 Zornitza Stark Marked gene: KRT13 as ready
Mendeliome v0.11252 KRT13 Zornitza Stark Gene: krt13 has been classified as Green List (High Evidence).
Mendeliome v0.11252 KRT13 Zornitza Stark Phenotypes for gene: KRT13 were changed from to White sponge nevus 2, MIM# 615785
Mendeliome v0.11251 KRT13 Zornitza Stark Publications for gene: KRT13 were set to
Mendeliome v0.11250 KRT13 Zornitza Stark Mode of inheritance for gene: KRT13 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11249 KRT13 Zornitza Stark reviewed gene: KRT13: Rating: GREEN; Mode of pathogenicity: None; Publications: 7493031, 14600690, 32758484, 29476668; Phenotypes: White sponge nevus 2, MIM# 615785; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11249 KRT16 Zornitza Stark Marked gene: KRT16 as ready
Mendeliome v0.11249 KRT16 Zornitza Stark Gene: krt16 has been classified as Green List (High Evidence).
Mendeliome v0.11249 KRT16 Zornitza Stark Phenotypes for gene: KRT16 were changed from to Palmoplantar keratoderma, nonepidermolytic, focal (MIM#613000); Pachyonychia congenita 1 (MIM#167200)
Mendeliome v0.11248 KRT16 Zornitza Stark Publications for gene: KRT16 were set to
Mendeliome v0.11247 KRT16 Zornitza Stark Mode of inheritance for gene: KRT16 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11246 KRT16 Zornitza Stark reviewed gene: KRT16: Rating: GREEN; Mode of pathogenicity: None; Publications: 8595410, 10839714; Phenotypes: Palmoplantar keratoderma, nonepidermolytic, focal (MIM#613000), Pachyonychia congenita 1 (MIM#167200); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11246 KRT18 Zornitza Stark Marked gene: KRT18 as ready
Mendeliome v0.11246 KRT18 Zornitza Stark Gene: krt18 has been classified as Red List (Low Evidence).
Mendeliome v0.11246 KRT18 Zornitza Stark Phenotypes for gene: KRT18 were changed from to Cirrhosis, cryptogenic , MIM#215600
Mendeliome v0.11245 KRT18 Zornitza Stark Publications for gene: KRT18 were set to
Mendeliome v0.11244 KRT18 Zornitza Stark Classified gene: KRT18 as Red List (low evidence)
Mendeliome v0.11244 KRT18 Zornitza Stark Gene: krt18 has been classified as Red List (Low Evidence).
Mendeliome v0.11243 KRT18 Zornitza Stark reviewed gene: KRT18: Rating: RED; Mode of pathogenicity: None; Publications: 9011570, 27689336, 20538000; Phenotypes: Cirrhosis, cryptogenic , MIM#215600; Mode of inheritance: None
Mendeliome v0.11243 KRT25 Zornitza Stark Marked gene: KRT25 as ready
Mendeliome v0.11243 KRT25 Zornitza Stark Gene: krt25 has been classified as Green List (High Evidence).
Mendeliome v0.11243 KRT25 Zornitza Stark Phenotypes for gene: KRT25 were changed from to Woolly hair, autosomal recessive 3 MIM#616760
Mendeliome v0.11242 KRT25 Zornitza Stark Publications for gene: KRT25 were set to
Mendeliome v0.11241 KRT25 Zornitza Stark Mode of inheritance for gene: KRT25 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11240 KRT4 Zornitza Stark Marked gene: KRT4 as ready
Mendeliome v0.11240 KRT4 Zornitza Stark Gene: krt4 has been classified as Green List (High Evidence).
Mendeliome v0.11240 KRT4 Zornitza Stark Phenotypes for gene: KRT4 were changed from to White sponge naevus 1, MIM# 193900
Mendeliome v0.11239 KRT4 Zornitza Stark Publications for gene: KRT4 were set to
Mendeliome v0.11238 KRT4 Zornitza Stark Mode of inheritance for gene: KRT4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11237 KRT4 Zornitza Stark reviewed gene: KRT4: Rating: GREEN; Mode of pathogenicity: None; Publications: 7493030, 10652003, 12828738; Phenotypes: White sponge naevus 1, MIM# 193900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11237 KRT74 Zornitza Stark Marked gene: KRT74 as ready
Mendeliome v0.11237 KRT74 Zornitza Stark Gene: krt74 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11237 KRT74 Zornitza Stark Phenotypes for gene: KRT74 were changed from to Ectodermal dysplasia 7, hair/nail type MIM#614929; Hypotrichosis 3 , MIM# 613981; Woolly hair, autosomal dominant, MIM# 194300
Mendeliome v0.11236 KRT74 Zornitza Stark Publications for gene: KRT74 were set to
Mendeliome v0.11235 KRT74 Zornitza Stark Mode of inheritance for gene: KRT74 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11234 KRT74 Zornitza Stark Classified gene: KRT74 as Amber List (moderate evidence)
Mendeliome v0.11234 KRT74 Zornitza Stark Gene: krt74 has been classified as Amber List (Moderate Evidence).
Hair disorders v0.58 KRT74 Zornitza Stark Marked gene: KRT74 as ready
Hair disorders v0.58 KRT74 Zornitza Stark Gene: krt74 has been classified as Amber List (Moderate Evidence).
Hair disorders v0.58 KRT74 Zornitza Stark Phenotypes for gene: KRT74 were changed from Hypotrichosis 3, 613981 to Hypotrichosis 3 , MIM# 613981; Woolly hair, autosomal dominant, MIM# 194300
Hair disorders v0.57 KRT74 Zornitza Stark Publications for gene: KRT74 were set to
Hair disorders v0.56 KRT74 Zornitza Stark Classified gene: KRT74 as Amber List (moderate evidence)
Hair disorders v0.56 KRT74 Zornitza Stark Gene: krt74 has been classified as Amber List (Moderate Evidence).
Hair disorders v0.55 KRT74 Zornitza Stark reviewed gene: KRT74: Rating: AMBER; Mode of pathogenicity: None; Publications: 21188418, 20346438, 21188418; Phenotypes: Hypotrichosis 3 , MIM# 613981, Woolly hair, autosomal dominant, MIM# 194300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ectodermal Dysplasia v0.67 KRT74 Zornitza Stark Marked gene: KRT74 as ready
Ectodermal Dysplasia v0.67 KRT74 Zornitza Stark Gene: krt74 has been classified as Red List (Low Evidence).
Ectodermal Dysplasia v0.67 KRT74 Zornitza Stark Classified gene: KRT74 as Red List (low evidence)
Ectodermal Dysplasia v0.67 KRT74 Zornitza Stark Gene: krt74 has been classified as Red List (Low Evidence).
Ectodermal Dysplasia v0.66 KRT74 Zornitza Stark reviewed gene: KRT74: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ectodermal dysplasia 7, hair/nail type MIM#614929; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11233 KRT74 Zornitza Stark reviewed gene: KRT74: Rating: AMBER; Mode of pathogenicity: None; Publications: 24714551, 21188418, 20346438, 21188418; Phenotypes: Ectodermal dysplasia 7, hair/nail type MIM#614929, Hypotrichosis 3 , MIM# 613981, Woolly hair, autosomal dominant, MIM# 194300; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11233 KRT75 Zornitza Stark Marked gene: KRT75 as ready
Mendeliome v0.11233 KRT75 Zornitza Stark Gene: krt75 has been classified as Red List (Low Evidence).
Mendeliome v0.11233 KRT75 Zornitza Stark Phenotypes for gene: KRT75 were changed from to {Pseudofolliculitis barbae, susceptibility to} 612318
Mendeliome v0.11232 KRT75 Zornitza Stark Classified gene: KRT75 as Red List (low evidence)
Mendeliome v0.11232 KRT75 Zornitza Stark Gene: krt75 has been classified as Red List (Low Evidence).
Mendeliome v0.11231 KRT75 Zornitza Stark reviewed gene: KRT75: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Pseudofolliculitis barbae, susceptibility to} 612318; Mode of inheritance: None
Mendeliome v0.11231 KRT81 Zornitza Stark Marked gene: KRT81 as ready
Mendeliome v0.11231 KRT81 Zornitza Stark Gene: krt81 has been classified as Green List (High Evidence).
Hair disorders v0.55 KRT81 Zornitza Stark Marked gene: KRT81 as ready
Hair disorders v0.55 KRT81 Zornitza Stark Gene: krt81 has been classified as Green List (High Evidence).
Hair disorders v0.55 KRT81 Zornitza Stark Phenotypes for gene: KRT81 were changed from Monilethrix, 158000 to Monilethrix, MIM# 158000
Hair disorders v0.54 KRT81 Zornitza Stark Publications for gene: KRT81 were set to 31332722
Hair disorders v0.53 KRT81 Zornitza Stark reviewed gene: KRT81: Rating: GREEN; Mode of pathogenicity: None; Publications: 9402962, 22628999; Phenotypes: Monilethrix, MIM# 158000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11231 KRT81 Zornitza Stark Phenotypes for gene: KRT81 were changed from to Monilethrix, MIM# 158000
Mendeliome v0.11230 KRT81 Zornitza Stark Publications for gene: KRT81 were set to
Mendeliome v0.11229 KRT81 Zornitza Stark Mode of inheritance for gene: KRT81 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11228 KRT81 Zornitza Stark reviewed gene: KRT81: Rating: GREEN; Mode of pathogenicity: None; Publications: 9402962, 22628999; Phenotypes: Monilethrix, MIM# 158000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.9 UNC80 Zornitza Stark Phenotypes for gene: UNC80 were changed from Persistent Hypotonia, Encephalopathy, Growth Retardation, and Severe Intellectual Disability to Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801; MONDO:0014777
Fetal anomalies v1.8 UNC80 Zornitza Stark Classified gene: UNC80 as Amber List (moderate evidence)
Fetal anomalies v1.8 UNC80 Zornitza Stark Gene: unc80 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.708 NARS2 Zornitza Stark Marked gene: NARS2 as ready
Mitochondrial disease v0.708 NARS2 Zornitza Stark Gene: nars2 has been classified as Green List (High Evidence).
Mitochondrial disease v0.708 NARS2 Zornitza Stark Phenotypes for gene: NARS2 were changed from to Combined oxidative phosphorylation deficiency 24 - MIM#616239; Deafness, autosomal recessive 94 - MIM#618434
Mitochondrial disease v0.707 NARS2 Zornitza Stark Publications for gene: NARS2 were set to
Mitochondrial disease v0.706 NARS2 Zornitza Stark Mode of inheritance for gene: NARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11228 NARS2 Zornitza Stark Marked gene: NARS2 as ready
Mendeliome v0.11228 NARS2 Zornitza Stark Gene: nars2 has been classified as Green List (High Evidence).
Mendeliome v0.11228 NARS2 Zornitza Stark Phenotypes for gene: NARS2 were changed from to Combined oxidative phosphorylation deficiency 24 - MIM#616239; Deafness, autosomal recessive 94 - MIM#618434
Mendeliome v0.11227 NARS2 Zornitza Stark Publications for gene: NARS2 were set to
Mendeliome v0.11226 NARS2 Zornitza Stark Mode of inheritance for gene: NARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1469 NARS2 Zornitza Stark Marked gene: NARS2 as ready
Genetic Epilepsy v0.1469 NARS2 Zornitza Stark Added comment: Comment when marking as ready: Refractory seizures are part of the phenotype.
Genetic Epilepsy v0.1469 NARS2 Zornitza Stark Gene: nars2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1469 NARS2 Zornitza Stark Phenotypes for gene: NARS2 were changed from to Combined oxidative phosphorylation deficiency 24 - MIM#616239
Genetic Epilepsy v0.1468 NARS2 Zornitza Stark Publications for gene: NARS2 were set to
Genetic Epilepsy v0.1467 NARS2 Zornitza Stark Mode of inheritance for gene: NARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11225 PNPLA3 Zornitza Stark Marked gene: PNPLA3 as ready
Mendeliome v0.11225 PNPLA3 Zornitza Stark Gene: pnpla3 has been classified as Red List (Low Evidence).
Mendeliome v0.11225 PNPLA3 Zornitza Stark Phenotypes for gene: PNPLA3 were changed from to Susceptibility to nonalcoholic fatty liver disease
Mendeliome v0.11224 PNPLA3 Zornitza Stark Publications for gene: PNPLA3 were set to
Mendeliome v0.11223 PNPLA3 Zornitza Stark Mode of inheritance for gene: PNPLA3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11222 PNPLA3 Zornitza Stark Classified gene: PNPLA3 as Red List (low evidence)
Mendeliome v0.11222 PNPLA3 Zornitza Stark Gene: pnpla3 has been classified as Red List (Low Evidence).
Microcephaly v1.113 NARS Zornitza Stark Marked gene: NARS as ready
Microcephaly v1.113 NARS Zornitza Stark Gene: nars has been classified as Green List (High Evidence).
Microcephaly v1.113 NARS Zornitza Stark Classified gene: NARS as Green List (high evidence)
Microcephaly v1.113 NARS Zornitza Stark Gene: nars has been classified as Green List (High Evidence).
Microcephaly v1.112 NARS Zornitza Stark Tag new gene name tag was added to gene: NARS.
Intellectual disability syndromic and non-syndromic v0.4546 NANS Zornitza Stark Marked gene: NANS as ready
Intellectual disability syndromic and non-syndromic v0.4546 NANS Zornitza Stark Gene: nans has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4546 NANS Zornitza Stark Phenotypes for gene: NANS were changed from to Spondyloepimetaphyseal dysplasia, Camera-Genevieve type - MIM#610442
Intellectual disability syndromic and non-syndromic v0.4545 NANS Zornitza Stark Publications for gene: NANS were set to
Intellectual disability syndromic and non-syndromic v0.4544 NANS Zornitza Stark Mode of inheritance for gene: NANS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11221 NANS Zornitza Stark Marked gene: NANS as ready
Mendeliome v0.11221 NANS Zornitza Stark Gene: nans has been classified as Green List (High Evidence).
Mendeliome v0.11221 NANS Zornitza Stark Phenotypes for gene: NANS were changed from to Spondyloepimetaphyseal dysplasia, Camera-Genevieve type - MIM#610442
Mendeliome v0.11220 NANS Zornitza Stark Publications for gene: NANS were set to
Mendeliome v0.11219 NANS Zornitza Stark Mode of inheritance for gene: NANS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.7 UNC80 Ain Roesley reviewed gene: UNC80: Rating: AMBER; Mode of pathogenicity: None; Publications: 26545877; Phenotypes: Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801, MONDO:0014777; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11218 S1PR2 Zornitza Stark Marked gene: S1PR2 as ready
Mendeliome v0.11218 S1PR2 Zornitza Stark Gene: s1pr2 has been classified as Green List (High Evidence).
Mendeliome v0.11218 S1PR2 Zornitza Stark Phenotypes for gene: S1PR2 were changed from to Deafness, autosomal recessive 68, MIM# 610419
Mendeliome v0.11217 S1PR2 Zornitza Stark Publications for gene: S1PR2 were set to
Mendeliome v0.11216 S1PR2 Zornitza Stark Mode of inheritance for gene: S1PR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11215 S1PR2 Zornitza Stark reviewed gene: S1PR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26805784, 29776397, 27383011; Phenotypes: Deafness, autosomal recessive 68, MIM# 610419; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.325 NALCN Zornitza Stark Phenotypes for gene: NALCN were changed from to Congenital contractures of the limbs and face, hypotonia, and developmental delay, MIM# 616266
Arthrogryposis v0.324 NALCN Zornitza Stark Publications for gene: NALCN were set to
Arthrogryposis v0.323 NALCN Zornitza Stark Mode of inheritance for gene: NALCN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Arthrogryposis v0.322 NALCN Zornitza Stark reviewed gene: NALCN: Rating: GREEN; Mode of pathogenicity: None; Publications: 25683120; Phenotypes: Congenital contractures of the limbs and face, hypotonia, and developmental delay, MIM# 616266; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v1.112 NALCN Zornitza Stark Marked gene: NALCN as ready
Microcephaly v1.112 NALCN Zornitza Stark Gene: nalcn has been classified as Green List (High Evidence).
Microcephaly v1.112 NALCN Zornitza Stark Classified gene: NALCN as Green List (high evidence)
Microcephaly v1.112 NALCN Zornitza Stark Gene: nalcn has been classified as Green List (High Evidence).
Mendeliome v0.11215 NALCN Zornitza Stark Marked gene: NALCN as ready
Mendeliome v0.11215 NALCN Zornitza Stark Gene: nalcn has been classified as Green List (High Evidence).
Mendeliome v0.11215 NALCN Zornitza Stark Phenotypes for gene: NALCN were changed from to Congenital contractures of the limbs and face, hypotonia, and developmental delay - MIM#616266; Hypotonia, infantile, with psychomotor retardation and characteristic facies 1 - MIM#615419
Mendeliome v0.11214 NALCN Zornitza Stark Publications for gene: NALCN were set to
Mendeliome v0.11213 NALCN Zornitza Stark Mode of inheritance for gene: NALCN was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11212 NAGS Zornitza Stark Marked gene: NAGS as ready
Mendeliome v0.11212 NAGS Zornitza Stark Gene: nags has been classified as Green List (High Evidence).
Mendeliome v0.11212 NAGS Zornitza Stark Phenotypes for gene: NAGS were changed from to N-acetylglutamate synthase deficiency - MIM#237310
Mendeliome v0.11211 NAGS Zornitza Stark Publications for gene: NAGS were set to
Mendeliome v0.11210 NAGS Zornitza Stark Mode of inheritance for gene: NAGS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1466 NACC1 Zornitza Stark Marked gene: NACC1 as ready
Genetic Epilepsy v0.1466 NACC1 Zornitza Stark Gene: nacc1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1466 NACC1 Zornitza Stark Phenotypes for gene: NACC1 were changed from to Neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination - MIM#617393
Genetic Epilepsy v0.1465 NACC1 Zornitza Stark Publications for gene: NACC1 were set to
Genetic Epilepsy v0.1464 NACC1 Zornitza Stark Mode of inheritance for gene: NACC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4543 NACC1 Zornitza Stark Phenotypes for gene: NACC1 were changed from to Neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination - MIM#617393
Genetic Epilepsy v0.1463 NACC1 Zornitza Stark reviewed gene: NACC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28132692; Phenotypes: Neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination - MIM#617393; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4542 NACC1 Zornitza Stark Publications for gene: NACC1 were set to
Intellectual disability syndromic and non-syndromic v0.4541 NACC1 Zornitza Stark Mode of inheritance for gene: NACC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4540 NACC1 Zornitza Stark reviewed gene: NACC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28132692; Phenotypes: Neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination - MIM#617393; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11209 NACC1 Zornitza Stark Marked gene: NACC1 as ready
Mendeliome v0.11209 NACC1 Zornitza Stark Gene: nacc1 has been classified as Green List (High Evidence).
Mendeliome v0.11209 NACC1 Zornitza Stark Phenotypes for gene: NACC1 were changed from to Neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination - MIM#617393
Mendeliome v0.11208 NACC1 Zornitza Stark Publications for gene: NACC1 were set to
Mendeliome v0.11207 NACC1 Zornitza Stark Mode of inheritance for gene: NACC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.7 NAA15 Zornitza Stark Publications for gene: NAA15 were set to 31127942
Fetal anomalies v1.6 NAA15 Zornitza Stark Classified gene: NAA15 as Green List (high evidence)
Fetal anomalies v1.6 NAA15 Zornitza Stark Gene: naa15 has been classified as Green List (High Evidence).
Fetal anomalies v1.5 NAA15 Zornitza Stark edited their review of gene: NAA15: Changed publications: 33557580
Fetal anomalies v1.5 NAA15 Zornitza Stark changed review comment from: Typically presents post-natally.; to: Congenital heart defects in 4 of 19 individuals reported with the neurodevelopmental syndrome.

PMID 33557580 - WES of 4511 patients with CHD identified 4 subjects with a rare LoF variant (allele frequency <0.00005) in the NAA15 gene, resulting in NAA15 haploinsufficiency. Parental analyses indicated that 3 of these LoF variants (p.Ser761*, p.Lys336Lys fs*6, and p.Arg470*) arose de novo in the probands. The inheritance of the p.Ala718fs variant is uncertain, as parental samples were unavailable. The authors also reference their previous studies identifying 2 other patients with CHD and LoF NAA15 heterozygous variants.
Fetal anomalies v1.5 NAA15 Zornitza Stark edited their review of gene: NAA15: Changed rating: GREEN
Fetal anomalies v1.5 NAA15 Zornitza Stark edited their review of gene: NAA15: Changed rating: AMBER
Intellectual disability syndromic and non-syndromic v0.4540 NAA15 Zornitza Stark Marked gene: NAA15 as ready
Intellectual disability syndromic and non-syndromic v0.4540 NAA15 Zornitza Stark Gene: naa15 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4540 NAA15 Zornitza Stark Phenotypes for gene: NAA15 were changed from to Intellectual developmental disorder, autosomal dominant 50, with behavioral abnormalities - MIM#617787
Intellectual disability syndromic and non-syndromic v0.4539 NAA15 Zornitza Stark Publications for gene: NAA15 were set to
Intellectual disability syndromic and non-syndromic v0.4538 NAA15 Zornitza Stark Mode of inheritance for gene: NAA15 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4537 NAA15 Zornitza Stark reviewed gene: NAA15: Rating: GREEN; Mode of pathogenicity: None; Publications: 33103328, 29656860, 31127942, 28191889, 33557580, 28990276; Phenotypes: Intellectual developmental disorder, autosomal dominant 50, with behavioral abnormalities - MIM#617787; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11206 NAA15 Zornitza Stark Marked gene: NAA15 as ready
Mendeliome v0.11206 NAA15 Zornitza Stark Gene: naa15 has been classified as Green List (High Evidence).
Mendeliome v0.11206 NAA15 Zornitza Stark Phenotypes for gene: NAA15 were changed from to Intellectual developmental disorder, autosomal dominant 50, with behavioral abnormalities - MIM#617787
Mendeliome v0.11205 NAA15 Zornitza Stark Publications for gene: NAA15 were set to
Mendeliome v0.11204 NAA15 Zornitza Stark Mode of inheritance for gene: NAA15 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.200 NAA15 Zornitza Stark Marked gene: NAA15 as ready
Congenital Heart Defect v0.200 NAA15 Zornitza Stark Gene: naa15 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.200 NAA15 Zornitza Stark Classified gene: NAA15 as Green List (high evidence)
Congenital Heart Defect v0.200 NAA15 Zornitza Stark Gene: naa15 has been classified as Green List (High Evidence).
Ciliopathies v1.27 SUFU Zornitza Stark Phenotypes for gene: SUFU were changed from Joubert syndrome 32, MIM#617757 to Joubert syndrome 32, MIM#617757; SUFU-related neurodevelopmental disorder, Joubert-like
Ciliopathies v1.26 SUFU Zornitza Stark Publications for gene: SUFU were set to 28965847
Ciliopathies v1.25 SUFU Zornitza Stark Mode of inheritance for gene: SUFU was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ciliopathies v1.24 SUFU Zornitza Stark Classified gene: SUFU as Green List (high evidence)
Ciliopathies v1.24 SUFU Zornitza Stark Gene: sufu has been classified as Green List (High Evidence).
Ciliopathies v1.23 SUFU Zornitza Stark edited their review of gene: SUFU: Added comment: Further 22 individuals reported with LoF variants in SUFU and a phenotype described as being on the mild end of JS. Clinical features included congenital oculomotor apraxia, hypotonia, ataxia and mild DD, and only a third manifested intellectual disability of variable severity. Brain MRI showed consistent findings characterised by vermis hypoplasia, superior cerebellar dysplasia and subtle-to-mild abnormalities of the superior cerebellar peduncles.; Changed rating: GREEN; Changed publications: 28965847, 34675124; Changed phenotypes: Joubert syndrome 32, MIM#617757, SUFU-related neurodevelopmental disorder, Joubert-like; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v1.21 SUFU Zornitza Stark Phenotypes for gene: SUFU were changed from Joubert syndrome 32, MIM#617757 to Joubert syndrome 32, MIM#617757; SUFU-related neurodevelopmental disorder, Joubert-like
Joubert syndrome and other neurological ciliopathies v1.20 SUFU Zornitza Stark Publications for gene: SUFU were set to 28965847
Joubert syndrome and other neurological ciliopathies v1.19 SUFU Zornitza Stark Mode of inheritance for gene: SUFU was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v1.18 SUFU Zornitza Stark Classified gene: SUFU as Green List (high evidence)
Joubert syndrome and other neurological ciliopathies v1.18 SUFU Zornitza Stark Gene: sufu has been classified as Green List (High Evidence).
Joubert syndrome and other neurological ciliopathies v1.17 SUFU Zornitza Stark edited their review of gene: SUFU: Changed phenotypes: SUFU-related neurodevelopmental disorder, Joubert-like, Joubert syndrome 32, MIM# 617757
Joubert syndrome and other neurological ciliopathies v1.17 SUFU Zornitza Stark edited their review of gene: SUFU: Added comment: Further 22 individuals reported with LoF variants in SUFU and a phenotype described as being on the mild end of JS.
Clinical features included congenital oculomotor apraxia, hypotonia, ataxia and mild DD, and only a third manifested intellectual disability of variable severity. Brain MRI showed consistent findings characterised by vermis hypoplasia, superior cerebellar dysplasia and subtle-to-mild abnormalities of the superior cerebellar peduncles.; Changed rating: GREEN; Changed publications: 34675124; Changed phenotypes: SUFU-related neurodevelopmental disorder, Joubert-like; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v1.17 SUFU Zornitza Stark Classified gene: SUFU as Amber List (moderate evidence)
Joubert syndrome and other neurological ciliopathies v1.17 SUFU Zornitza Stark Gene: sufu has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11203 NARS2 Krithika Murali reviewed gene: NARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25385316, 25807530, 30327238, 28077841; Phenotypes: Combined oxidative phosphorylation deficiency 24 - MIM#616239, ?Deafness, autosomal recessive 94 - MIM#618434; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.705 NARS2 Krithika Murali reviewed gene: NARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25385316, 25807530, 30327238, 28077841; Phenotypes: Combined oxidative phosphorylation deficiency 24 - MIM#616239, ?Deafness, autosomal recessive 94 - MIM#618434; Mode of inheritance: None
Genetic Epilepsy v0.1463 NARS2 Krithika Murali reviewed gene: NARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25385316, 25807530, 30327238, 28077841; Phenotypes: Combined oxidative phosphorylation deficiency 24 - MIM#616239, ?Deafness, autosomal recessive 94 - MIM#618434; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Palmoplantar Keratoderma and Erythrokeratoderma v0.111 KRT83 Zornitza Stark Marked gene: KRT83 as ready
Palmoplantar Keratoderma and Erythrokeratoderma v0.111 KRT83 Zornitza Stark Gene: krt83 has been classified as Red List (Low Evidence).
Palmoplantar Keratoderma and Erythrokeratoderma v0.111 KRT83 Zornitza Stark gene: KRT83 was added
gene: KRT83 was added to Palmoplantar Keratoderma and Erythrokeratoderma. Sources: Expert Review
Mode of inheritance for gene: KRT83 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KRT83 were set to 27965375
Phenotypes for gene: KRT83 were set to Erythrokeratodermia variabilis et progressiva 5, MIM# 617756
Review for gene: KRT83 was set to RED
Added comment: Single family reported.
Sources: Expert Review
Hair disorders v0.53 KRT83 Zornitza Stark Publications for gene: KRT83 were set to 31332722
Hair disorders v0.52 KRT83 Zornitza Stark Marked gene: KRT83 as ready
Hair disorders v0.52 KRT83 Zornitza Stark Gene: krt83 has been classified as Amber List (Moderate Evidence).
Hair disorders v0.52 KRT83 Zornitza Stark Classified gene: KRT83 as Amber List (moderate evidence)
Hair disorders v0.52 KRT83 Zornitza Stark Gene: krt83 has been classified as Amber List (Moderate Evidence).
Hair disorders v0.51 KRT83 Zornitza Stark reviewed gene: KRT83: Rating: AMBER; Mode of pathogenicity: None; Publications: 15744029, 25557232; Phenotypes: Monilethrix , MIM#158000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11203 KRT83 Zornitza Stark Marked gene: KRT83 as ready
Mendeliome v0.11203 KRT83 Zornitza Stark Gene: krt83 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11203 KRT83 Zornitza Stark Phenotypes for gene: KRT83 were changed from to Erythrokeratodermia variabilis et progressiva 5, MIM# 617756; Monilethrix , MIM#158000
Mendeliome v0.11202 KRT83 Zornitza Stark Publications for gene: KRT83 were set to
Mendeliome v0.11201 KRT83 Zornitza Stark Mode of inheritance for gene: KRT83 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11200 KRT83 Zornitza Stark Classified gene: KRT83 as Amber List (moderate evidence)
Mendeliome v0.11200 KRT83 Zornitza Stark Gene: krt83 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11199 KRT83 Zornitza Stark reviewed gene: KRT83: Rating: AMBER; Mode of pathogenicity: None; Publications: 27965375, 15744029, 25557232; Phenotypes: Erythrokeratodermia variabilis et progressiva 5, MIM# 617756, Monilethrix , MIM#158000; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11199 PNPLA3 Paul De Fazio reviewed gene: PNPLA3: Rating: RED; Mode of pathogenicity: None; Publications: 18820647; Phenotypes: Susceptibility to nonalcoholic fatty liver disease; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.11199 KRT10 Zornitza Stark Marked gene: KRT10 as ready
Mendeliome v0.11199 KRT10 Zornitza Stark Gene: krt10 has been classified as Green List (High Evidence).
Mendeliome v0.11199 KRT10 Zornitza Stark Phenotypes for gene: KRT10 were changed from to Epidermolytic hyperkeratosis, MIM#113800; Ichthyosis with confetti, MIM#609165; Ichthyosis, cyclic, with epidermolytic hyperkeratosis, MIM#607602
Mendeliome v0.11198 KRT10 Zornitza Stark Publications for gene: KRT10 were set to
Mendeliome v0.11197 KRT10 Zornitza Stark Mode of pathogenicity for gene: KRT10 was changed from Other to None
Mendeliome v0.11196 KRT10 Zornitza Stark Mode of pathogenicity for gene: KRT10 was changed from to Other
Mendeliome v0.11195 KRT10 Zornitza Stark Mode of inheritance for gene: KRT10 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11194 ERLEC1 Bryony Thompson Marked gene: ERLEC1 as ready
Mendeliome v0.11194 ERLEC1 Bryony Thompson Gene: erlec1 has been classified as Green List (High Evidence).
Mendeliome v0.11194 ERLEC1 Bryony Thompson Phenotypes for gene: ERLEC1 were changed from Class III malocclusion to autosomal dominant prognathism MONDO:0008312
Mendeliome v0.11193 ERBB4 Bryony Thompson Phenotypes for gene: ERBB4 were changed from Amyotrophic lateral sclerosis 19, MIM# MIM#615515; Intellectual disability to Amyotrophic lateral sclerosis 19, MIM# MIM#615515; Intellectual disability MONDO:0001071
Fetal anomalies v1.5 EFNB1 Bryony Thompson Added comment: Comment on mode of inheritance: X-LINKED: heterozygous females demonstrate more severe disease than hemizygous males
Fetal anomalies v1.5 EFNB1 Bryony Thompson Mode of inheritance for gene: EFNB1 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 Other
Clefting disorders v0.177 EFNB1 Bryony Thompson Added comment: Comment on mode of inheritance: X-LINKED: heterozygous females demonstrate more severe disease than hemizygous males
Clefting disorders v0.177 EFNB1 Bryony Thompson Mode of inheritance for gene: EFNB1 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 Other
Congenital diaphragmatic hernia v1.6 EFNB1 Bryony Thompson Added comment: Comment on mode of inheritance: X-LINKED: heterozygous females demonstrate more severe disease than hemizygous males
Congenital diaphragmatic hernia v1.6 EFNB1 Bryony Thompson Mode of inheritance for gene: EFNB1 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 Other
Fetal anomalies v1.4 NARS Krithika Murali gene: NARS was added
gene: NARS was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: NARS was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NARS were set to 32738225; 32788587
Phenotypes for gene: NARS were set to Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, autosomal recessive - MIM#619091; Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, autosomal dominant - MIM#619092
Review for gene: NARS was set to GREEN
Added comment: HGNC approved gene symbol - NARS1

Both mono allelic and biallelic variants associated with a progressive neurological disorder with onset in infancy. Antenatal features reported.

PMID 32738225 - reports roband with de novo heterozygous variant - IUGR and oligohydramnios noted prenatally. At birth noted to have low weight and OFC for gestational age. Proband with homozygous variant diagnosed with microcephaly, seizures and FTT in the neonatal period. Proband with compound het variants born with a low weight (-2.38 SD) and height (-3.76 SD) for gestational age. Review of supplementary material table - microcephaly at birth reported in 17 unrelated families.
Sources: Literature
Microcephaly v1.111 NARS Krithika Murali gene: NARS was added
gene: NARS was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: NARS was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NARS were set to 32738225; 32788587
Phenotypes for gene: NARS were set to Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, autosomal recessive - MIM#619091; Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, autosomal dominant - MIM#619092
Review for gene: NARS was set to GREEN
Added comment: HGNC approved gene symbol - NARS1

Both mono allelic and biallelic variants associated with a progressive neurological disorder with onset in infancy. Microcephaly a commonly reported feature.
Sources: Literature
Mendeliome v0.11192 NANS Krithika Murali reviewed gene: NANS: Rating: GREEN; Mode of pathogenicity: None; Publications: 8152878, 15726110, 8723082, 27213289, 7551156; Phenotypes: Spondyloepimetaphyseal dysplasia, Camera-Genevieve type - MIM#610442; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4537 NANS Krithika Murali reviewed gene: NANS: Rating: GREEN; Mode of pathogenicity: None; Publications: 8152878, 15726110, 8723082, 27213289, 7551156; Phenotypes: Spondyloepimetaphyseal dysplasia, Camera-Genevieve type - MIM#610442; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.111 NALCN Krithika Murali gene: NALCN was added
gene: NALCN was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: NALCN was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NALCN were set to 25683120; 23749988; 24075186; 30167850
Phenotypes for gene: NALCN were set to Congenital contractures of the limbs and face, hypotonia, and developmental delay - MIM#616266; Hypotonia, infantile, with psychomotor retardation and characteristic facies 1 - MIM#615419
Review for gene: NALCN was set to GREEN
Added comment: Monoallelic NALCN missense variants reported in individuals with congenital contractures of the limbs and face, hypotonia, and developmental delay.

Biallelic NALCN variants cause severe infantile hypotonia with psychomotor retardation and characteristic facial features. Microcephaly a reported feature. PMID: 30167850 report new cases with balletic variants and review previously published cases noting microcephaly in 14/21 individuals.
Sources: Literature
Mendeliome v0.11192 NALCN Krithika Murali reviewed gene: NALCN: Rating: GREEN; Mode of pathogenicity: None; Publications: 25683120, 23749988, 24075186, 30167850; Phenotypes: Congenital contractures of the limbs and face, hypotonia, and developmental delay - MIM#616266, Hypotonia, infantile, with psychomotor retardation and characteristic facies 1 - MIM#615419; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Craniosynostosis v1.35 IRX5 Zornitza Stark Publications for gene: IRX5 were set to 22581230
Craniosynostosis v1.34 IRX5 Zornitza Stark Classified gene: IRX5 as Green List (high evidence)
Craniosynostosis v1.34 IRX5 Zornitza Stark Gene: irx5 has been classified as Green List (High Evidence).
Craniosynostosis v1.33 IRX5 Zornitza Stark reviewed gene: IRX5: Rating: GREEN; Mode of pathogenicity: None; Publications: 22581230, 27453922, 34899143; Phenotypes: Hamamy syndrome, MIM# 611174; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.4 IRX5 Zornitza Stark Classified gene: IRX5 as Green List (high evidence)
Fetal anomalies v1.4 IRX5 Zornitza Stark Gene: irx5 has been classified as Green List (High Evidence).
Fetal anomalies v1.3 IRX5 Zornitza Stark edited their review of gene: IRX5: Added comment: Third family with Hamamy syndrome and homozygous missense variant reported, p.Arg168His. Two cousins, >4 meioses, good segregation data.; Changed rating: GREEN; Changed publications: 22581230, 27453922, 34899143
Intellectual disability syndromic and non-syndromic v0.4537 IRX5 Zornitza Stark Publications for gene: IRX5 were set to 22581230; 27453922
Intellectual disability syndromic and non-syndromic v0.4536 IRX5 Zornitza Stark Classified gene: IRX5 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4536 IRX5 Zornitza Stark Gene: irx5 has been classified as Green List (High Evidence).
Mendeliome v0.11192 NAGS Krithika Murali reviewed gene: NAGS: Rating: GREEN; Mode of pathogenicity: None; Publications: 12594532, 17421020, 12459178, 12754705, 9877039; Phenotypes: N-acetylglutamate synthase deficiency - MIM#237310; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4535 IRX5 Zornitza Stark edited their review of gene: IRX5: Added comment: Third family with Hamamy syndrome and homozygous missense variant reported, p.Arg168His. Two cousins, >4 meioses, good segregation data. Intellectual disability.; Changed rating: GREEN; Changed publications: 22581230, 27453922, 34899143
Mendeliome v0.11192 IRX5 Zornitza Stark Publications for gene: IRX5 were set to 27453922; 33891002; 28041643; 32045705; 22581230; 17230486
Mendeliome v0.11191 IRX5 Zornitza Stark Mode of pathogenicity for gene: IRX5 was changed from to None
Mendeliome v0.11190 IRX5 Zornitza Stark Classified gene: IRX5 as Green List (high evidence)
Mendeliome v0.11190 IRX5 Zornitza Stark Gene: irx5 has been classified as Green List (High Evidence).
Mendeliome v0.11189 IRX5 Zornitza Stark edited their review of gene: IRX5: Added comment: Third family with Hamamy syndrome and homozygous missense variant reported, p.Arg168His. Two cousins, >4 meioses, good segregation data.

4th family as part of large heterogenous cohort of consanguineous families also reported with homozygous frameshift (last exon), but limited phenotypic data.; Changed rating: GREEN; Changed publications: 22581230, 27453922, 34899143
Mendeliome v0.11189 NACC1 Krithika Murali reviewed gene: NACC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28132692; Phenotypes: Neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination - MIM#617393; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.199 NAA15 Krithika Murali Deleted their comment
Congenital Heart Defect v0.199 NAA15 Krithika Murali edited their review of gene: NAA15: Added comment: Monoallelic variants associated with syndromic ID. At least 47 individuals from 42 unrelated families in the published literature. Phenotypic features reported include:

- ID (all)
- Mild dysmorphic features (20/30)
- ASD/ADHD/behavioural issues (30/33)
- Skeletal and connective tissue anomalies (10/22)
- Congenital heart defects (4/19)
- Hypertrophic cardiomyopathy (paediatric onset) - 2 unrelated individuals (PMID: 33103328)

In addition:

PMID 33557580 - WES of 4511 patients with CHD identified 4 subjects with a rare LoF variant (allele frequency <0.00005) in the NAA15 gene, resulting in NAA15 haploinsufficiency. Parental analyses indicated that 3 of these LoF variants (p.Ser761*, p.Lys336Lys fs*6, and p.Arg470*) arose de novo in the probands. The inheritance of the p.Ala718fs variant is uncertain, as parental samples were unavailable. The authors also reference their previous studies identifying 2 other patients with CHD and LoF NAA15 heterozygous variants.; Changed phenotypes: Intellectual developmental disorder, autosomal dominant 50, with behavioral abnormalities - MIM#617787, congenital heart defect
Mendeliome v0.11189 NAA15 Krithika Murali reviewed gene: NAA15: Rating: GREEN; Mode of pathogenicity: None; Publications: 33103328, 29656860, 31127942, 28191889, 33557580, 28990276; Phenotypes: Intellectual developmental disorder, autosomal dominant 50, with behavioral abnormalities - MIM#617787; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.199 NAA15 Krithika Murali gene: NAA15 was added
gene: NAA15 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: NAA15 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NAA15 were set to 33103328; 29656860; 31127942; 28191889; 33557580; 28990276
Phenotypes for gene: NAA15 were set to Intellectual developmental disorder, autosomal dominant 50, with behavioral abnormalities - MIM#617787
Review for gene: NAA15 was set to GREEN
Added comment: Monoallelic variants associated with syndromic ID. At least 47 individuals from 42 unrelated families in the published literature. Phenotypic features reported include:

- ID (all)
- Mild dysmorphic features (20/30)
- ASD/ADHD/behavioural issues (30/33)
- Skeletal and connective tissue anomalies (10/22)
- Congenital heart defects (4/19)
- Hypertrophic cardiomyopathy (paediatric onset) - 2 unrelated individuals (PMID: 33103328)

In addition:

PMID 33557580 - WES of 4511 patients with CHD identified 4 subjects with a rare LoF variant (allele frequency <0.00005) in the NAA15 gene, resulting in NAA15 haploinsufficiency. Parental analyses indicated that 3 of these LoF variants (p.Ser761*, p.Lys336Lys fs*6, and p.Arg470*) arose de novo in the probands. The inheritance of the p.Ala718fs variant is uncertain, as parental samples were unavailable. The authors also reference their previous studies identifying 2 other patients with CHD and LoF NAA15 heterozygous variants.
Sources: Literature
Callosome v0.364 EARS2 Bryony Thompson Marked gene: EARS2 as ready
Callosome v0.364 EARS2 Bryony Thompson Gene: ears2 has been classified as Green List (High Evidence).
Callosome v0.364 EARS2 Bryony Thompson Phenotypes for gene: EARS2 were changed from to Leigh syndrome MONDO:0009723; Combined oxidative phosphorylation deficiency 12 MIM#614924; leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome MONDO:0013971
Callosome v0.363 EARS2 Bryony Thompson Publications for gene: EARS2 were set to
Callosome v0.362 EARS2 Bryony Thompson Mode of inheritance for gene: EARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Callosome v0.361 EARS2 Bryony Thompson reviewed gene: EARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22492562, 23008233, 25854774, 26619324, 26893310, 27206875, 27571996, 27117034; Phenotypes: Leigh syndrome MONDO:0009723, Combined oxidative phosphorylation deficiency 12 MIM#614924, leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome MONDO:0013971; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic Epilepsy v0.1463 EARS2 Bryony Thompson Marked gene: EARS2 as ready
Genetic Epilepsy v0.1463 EARS2 Bryony Thompson Gene: ears2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1463 EARS2 Bryony Thompson Phenotypes for gene: EARS2 were changed from to Leigh syndrome MONDO:0009723; Combined oxidative phosphorylation deficiency 12 MIM#614924; leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome MONDO:0013971
Genetic Epilepsy v0.1462 EARS2 Bryony Thompson Publications for gene: EARS2 were set to
Genetic Epilepsy v0.1461 EARS2 Bryony Thompson Mode of inheritance for gene: EARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1460 EARS2 Bryony Thompson reviewed gene: EARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22492562, 23008233, 25854774, 26619324, 26893310, 27206875, 27571996, 27117034; Phenotypes: Leigh syndrome MONDO:0009723, Combined oxidative phosphorylation deficiency 12 MIM#614924, leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome MONDO:0013971; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mitochondrial disease v0.705 EARS2 Bryony Thompson Marked gene: EARS2 as ready
Mitochondrial disease v0.705 EARS2 Bryony Thompson Gene: ears2 has been classified as Green List (High Evidence).
Mitochondrial disease v0.705 EARS2 Bryony Thompson Phenotypes for gene: EARS2 were changed from to Leigh syndrome MONDO:0009723; Combined oxidative phosphorylation deficiency 12 MIM#614924; leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome MONDO:0013971
Mitochondrial disease v0.704 EARS2 Bryony Thompson Publications for gene: EARS2 were set to
Mitochondrial disease v0.703 EARS2 Bryony Thompson Mode of inheritance for gene: EARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.702 EARS2 Bryony Thompson reviewed gene: EARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22492562, 23008233, 25854774, 26619324, 26893310, 27206875, 27571996, 27117034; Phenotypes: Leigh syndrome MONDO:0009723, Combined oxidative phosphorylation deficiency 12 MIM#614924, leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome MONDO:0013971; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11189 EARS2 Bryony Thompson Marked gene: EARS2 as ready
Mendeliome v0.11189 EARS2 Bryony Thompson Gene: ears2 has been classified as Green List (High Evidence).
Mendeliome v0.11189 EARS2 Bryony Thompson Phenotypes for gene: EARS2 were changed from to Leigh syndrome MONDO:0009723; Combined oxidative phosphorylation deficiency 12 MIM#614924; leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome MONDO:0013971
Mendeliome v0.11188 EARS2 Bryony Thompson Publications for gene: EARS2 were set to
Mendeliome v0.11187 EARS2 Bryony Thompson Mode of inheritance for gene: EARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11186 EARS2 Bryony Thompson reviewed gene: EARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22492562, 23008233, 25854774, 26619324, 26893310, 27206875, 27571996, 27117034; Phenotypes: Leigh syndrome MONDO:0009723, Combined oxidative phosphorylation deficiency 12 MIM#614924, leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome MONDO:0013971; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11186 KRT8 Zornitza Stark Mode of inheritance for gene: KRT8 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11185 KRT8 Zornitza Stark Marked gene: KRT8 as ready
Mendeliome v0.11185 KRT8 Zornitza Stark Gene: krt8 has been classified as Red List (Low Evidence).
Mendeliome v0.11185 KRT8 Zornitza Stark Phenotypes for gene: KRT8 were changed from to Cirrhosis, cryptogenic, MIM# 215600
Mendeliome v0.11184 KRT8 Zornitza Stark Publications for gene: KRT8 were set to
Mendeliome v0.11183 KRT8 Zornitza Stark Mode of inheritance for gene: KRT8 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11182 KRT8 Zornitza Stark Classified gene: KRT8 as Red List (low evidence)
Mendeliome v0.11182 KRT8 Zornitza Stark Gene: krt8 has been classified as Red List (Low Evidence).
Mendeliome v0.11181 KRT85 Zornitza Stark Marked gene: KRT85 as ready
Mendeliome v0.11181 KRT85 Zornitza Stark Gene: krt85 has been classified as Green List (High Evidence).
Mendeliome v0.11181 KRT85 Zornitza Stark Phenotypes for gene: KRT85 were changed from to Ectodermal dysplasia 4, hair/nail type MIM#602032
Mendeliome v0.11180 KRT85 Zornitza Stark Publications for gene: KRT85 were set to
Mendeliome v0.11179 KRT85 Zornitza Stark Mode of inheritance for gene: KRT85 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11178 KRT86 Zornitza Stark Marked gene: KRT86 as ready
Mendeliome v0.11178 KRT86 Zornitza Stark Gene: krt86 has been classified as Green List (High Evidence).
Hair disorders v0.51 KRT86 Zornitza Stark Marked gene: KRT86 as ready
Hair disorders v0.51 KRT86 Zornitza Stark Gene: krt86 has been classified as Green List (High Evidence).
Hair disorders v0.51 KRT86 Zornitza Stark Phenotypes for gene: KRT86 were changed from Monilethrix, 158000 to Monilethrix, MIM# 158000
Mendeliome v0.11178 KRT86 Zornitza Stark Phenotypes for gene: KRT86 were changed from to Monilethrix, MIM# 158000
Hair disorders v0.50 KRT86 Zornitza Stark reviewed gene: KRT86: Rating: GREEN; Mode of pathogenicity: None; Publications: 9241275; Phenotypes: Monilethrix, MIM# 158000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11177 KRT86 Zornitza Stark Publications for gene: KRT86 were set to
Mendeliome v0.11176 KRT86 Zornitza Stark Mode of inheritance for gene: KRT86 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11175 KRT86 Zornitza Stark reviewed gene: KRT86: Rating: GREEN; Mode of pathogenicity: None; Publications: 9241275; Phenotypes: Monilethrix, MIM# 158000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11175 KRT9 Zornitza Stark Marked gene: KRT9 as ready
Mendeliome v0.11175 KRT9 Zornitza Stark Gene: krt9 has been classified as Green List (High Evidence).
Mendeliome v0.11175 KRT9 Zornitza Stark Phenotypes for gene: KRT9 were changed from to Palmoplantar keratoderma, epidermolytic (MIM#144200)
Mendeliome v0.11174 KRT9 Zornitza Stark Publications for gene: KRT9 were set to
Mendeliome v0.11173 KRT9 Zornitza Stark Mode of inheritance for gene: KRT9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11172 KRT9 Zornitza Stark reviewed gene: KRT9: Rating: GREEN; Mode of pathogenicity: None; Publications: 31525823, 29044727, 7512862; Phenotypes: Palmoplantar keratoderma, epidermolytic (MIM#144200); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11172 KY Zornitza Stark Marked gene: KY as ready
Mendeliome v0.11172 KY Zornitza Stark Gene: ky has been classified as Green List (High Evidence).
Mendeliome v0.11172 KY Zornitza Stark Phenotypes for gene: KY were changed from to Myopathy, myofibrillar, 7, MIM#617114
Mendeliome v0.11171 KY Zornitza Stark Publications for gene: KY were set to
Mendeliome v0.11170 KY Zornitza Stark Mode of inheritance for gene: KY was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11169 KY Zornitza Stark reviewed gene: KY: Rating: GREEN; Mode of pathogenicity: None; Publications: 11136708, 27485408, 27484770, 30591934; Phenotypes: Myopathy, myofibrillar, 7, MIM#617114; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11169 KYNU Zornitza Stark Marked gene: KYNU as ready
Mendeliome v0.11169 KYNU Zornitza Stark Gene: kynu has been classified as Green List (High Evidence).
Mendeliome v0.11169 KYNU Zornitza Stark Phenotypes for gene: KYNU were changed from to Hydroxykynureninuria MIM#236800; Vertebral, cardiac, renal, and limb defects syndrome 2 MIM#617661; Disorders of histidine, tryptophan or lysine metabolism
Mendeliome v0.11168 KYNU Zornitza Stark Publications for gene: KYNU were set to
Mendeliome v0.11167 KYNU Zornitza Stark Mode of inheritance for gene: KYNU was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11166 JAG1 Zornitza Stark Marked gene: JAG1 as ready
Mendeliome v0.11166 JAG1 Zornitza Stark Gene: jag1 has been classified as Green List (High Evidence).
Mendeliome v0.11166 JAG1 Zornitza Stark Phenotypes for gene: JAG1 were changed from to Alagille syndrome 1, MIM# 118450; Charcot-Marie-Tooth disease, axonal, type 2HH, MIM# 619574
Mendeliome v0.11165 JAG1 Zornitza Stark Publications for gene: JAG1 were set to
Mendeliome v0.11164 JAG1 Zornitza Stark Mode of inheritance for gene: JAG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11163 JAG1 Zornitza Stark changed review comment from: Two unrelated families reported with CMT type 2. Affected individuals in both families exhibited severe vocal fold paresis, a rare feature of peripheral nerve disease that can be life-threatening. Studies of mutant protein posttranslational modification and localization indicated that the mutations (p.Ser577Arg, p.Ser650Pro) impair protein glycosylation and reduce JAG1 cell surface expression. Mice harboring heterozygous CMT2-associated mutations exhibited mild peripheral neuropathy, and homozygous expression resulted in embryonic lethality by midgestation. Pre-existing rat model.
Sources: Literature; to: Association with Alagille is very well established.

Two unrelated families reported with CMT type 2. Affected individuals in both families exhibited severe vocal fold paresis, a rare feature of peripheral nerve disease that can be life-threatening. Studies of mutant protein posttranslational modification and localization indicated that the mutations (p.Ser577Arg, p.Ser650Pro) impair protein glycosylation and reduce JAG1 cell surface expression. Mice harboring heterozygous CMT2-associated mutations exhibited mild peripheral neuropathy, and homozygous expression resulted in embryonic lethality by midgestation. Pre-existing rat model.
Sources: Literature
Mendeliome v0.11163 JAG1 Zornitza Stark edited their review of gene: JAG1: Changed phenotypes: Alagille syndrome 1, MIM# 118450, Charcot-Marie-Tooth disease, axonal, type 2HH, MIM# 619574
Mendeliome v0.11163 JUP Zornitza Stark Marked gene: JUP as ready
Mendeliome v0.11163 JUP Zornitza Stark Gene: jup has been classified as Green List (High Evidence).
Mendeliome v0.11163 JUP Zornitza Stark Phenotypes for gene: JUP were changed from to Arrhythmogenic right ventricular dysplasia 12, MIM# 611528; Naxos disease, MIM# 601214
Mendeliome v0.11162 JUP Zornitza Stark Publications for gene: JUP were set to
Mendeliome v0.11161 JUP Zornitza Stark Mode of inheritance for gene: JUP was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11160 JUP Zornitza Stark edited their review of gene: JUP: Changed phenotypes: Arrhythmogenic right ventricular dysplasia 12, MIM# 611528, Naxos disease, MIM# 601214
Mendeliome v0.11160 JUP Zornitza Stark reviewed gene: JUP: Rating: GREEN; Mode of pathogenicity: None; Publications: 2945574, 21668431, 2945574, 9610536, 18937352, 10902626, 15851108, 27170944, 11691526, 16893920, 29802319, 31275992, 25820315, 25820315, 25765472, 25705887, 25087486, 21668431, 20130592, 17924338, 20031617, 10902626, 20130592, 21320868, 32212272; Phenotypes: Arrhythmogenic right ventricular dysplasia 12, MIM# 611528; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11160 JPT1 Zornitza Stark Marked gene: JPT1 as ready
Mendeliome v0.11160 JPT1 Zornitza Stark Gene: jpt1 has been classified as Red List (Low Evidence).
Mendeliome v0.11160 JPT1 Zornitza Stark Classified gene: JPT1 as Red List (low evidence)
Mendeliome v0.11160 JPT1 Zornitza Stark Gene: jpt1 has been classified as Red List (Low Evidence).
Mendeliome v0.11159 JAK2 Zornitza Stark Marked gene: JAK2 as ready
Mendeliome v0.11159 JAK2 Zornitza Stark Gene: jak2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11159 JAK2 Zornitza Stark Phenotypes for gene: JAK2 were changed from to Thrombocythaemia 3, MIM# 614521
Mendeliome v0.11158 JAK2 Zornitza Stark Publications for gene: JAK2 were set to
Mendeliome v0.11157 JAK2 Zornitza Stark Mode of inheritance for gene: JAK2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11156 JAK2 Zornitza Stark Classified gene: JAK2 as Amber List (moderate evidence)
Mendeliome v0.11156 JAK2 Zornitza Stark Gene: jak2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11155 JAK2 Zornitza Stark Tag somatic tag was added to gene: JAK2.
Mendeliome v0.11155 JAK2 Zornitza Stark reviewed gene: JAK2: Rating: AMBER; Mode of pathogenicity: None; Publications: 22397670, 35129130; Phenotypes: Thrombocythaemia 3, MIM# 614521; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11155 ZNF644 Zornitza Stark Marked gene: ZNF644 as ready
Mendeliome v0.11155 ZNF644 Zornitza Stark Gene: znf644 has been classified as Green List (High Evidence).
Mendeliome v0.11155 ZNF644 Zornitza Stark Phenotypes for gene: ZNF644 were changed from to Myopia 21, autosomal dominant, MIM# 614167
Mendeliome v0.11154 ZNF644 Zornitza Stark Publications for gene: ZNF644 were set to
Mendeliome v0.11153 ZNF644 Zornitza Stark Mode of inheritance for gene: ZNF644 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11152 ZNF644 Zornitza Stark reviewed gene: ZNF644: Rating: GREEN; Mode of pathogenicity: None; Publications: 21695231, 30834109, 31560770, 24991186; Phenotypes: Myopia 21, autosomal dominant, MIM# 614167; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11152 ZNF513 Zornitza Stark Marked gene: ZNF513 as ready
Mendeliome v0.11152 ZNF513 Zornitza Stark Gene: znf513 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11152 ZNF513 Zornitza Stark Phenotypes for gene: ZNF513 were changed from to Retinitis pigmentosa 58 MIM#613617
Mendeliome v0.11151 ZNF513 Zornitza Stark Publications for gene: ZNF513 were set to
Mendeliome v0.11150 ZNF513 Zornitza Stark Mode of inheritance for gene: ZNF513 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11149 ZNF513 Zornitza Stark Classified gene: ZNF513 as Amber List (moderate evidence)
Mendeliome v0.11149 ZNF513 Zornitza Stark Gene: znf513 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11148 ZNF513 Zornitza Stark reviewed gene: ZNF513: Rating: AMBER; Mode of pathogenicity: None; Publications: 20797688; Phenotypes: Retinitis pigmentosa 58 MIM#613617; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinitis pigmentosa v0.107 ZNF408 Zornitza Stark Marked gene: ZNF408 as ready
Retinitis pigmentosa v0.107 ZNF408 Zornitza Stark Gene: znf408 has been classified as Green List (High Evidence).
Retinitis pigmentosa v0.107 ZNF408 Zornitza Stark Phenotypes for gene: ZNF408 were changed from Retinitis pigmentosa 72; Familial exudative vitreoretinopathy (FEVR) to Retinitis pigmentosa 72, MIM# 616469
Retinitis pigmentosa v0.106 ZNF408 Zornitza Stark Publications for gene: ZNF408 were set to
Retinitis pigmentosa v0.105 ZNF408 Zornitza Stark Mode of inheritance for gene: ZNF408 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Retinitis pigmentosa v0.104 ZNF408 Zornitza Stark reviewed gene: ZNF408: Rating: GREEN; Mode of pathogenicity: None; Publications: 25882705, 34259982, 28095122; Phenotypes: Retinitis pigmentosa 72, MIM# 616469; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11148 ZNF408 Zornitza Stark Marked gene: ZNF408 as ready
Mendeliome v0.11148 ZNF408 Zornitza Stark Gene: znf408 has been classified as Green List (High Evidence).
Mendeliome v0.11148 ZNF408 Zornitza Stark Phenotypes for gene: ZNF408 were changed from to Exudative vitreoretinopathy 6, MIM# 616468; Retinitis pigmentosa 72, MIM# 616469
Mendeliome v0.11147 ZNF408 Zornitza Stark Publications for gene: ZNF408 were set to
Mendeliome v0.11146 ZNF408 Zornitza Stark Mode of inheritance for gene: ZNF408 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11145 ZNF408 Zornitza Stark reviewed gene: ZNF408: Rating: GREEN; Mode of pathogenicity: None; Publications: 23716654, 32530348, 32097476, 32238352, 30998249, 29982478, 25882705, 34259982, 28095122; Phenotypes: Exudative vitreoretinopathy 6, MIM# 616468, Retinitis pigmentosa 72, MIM# 616469; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11145 ZNF335 Zornitza Stark Marked gene: ZNF335 as ready
Mendeliome v0.11145 ZNF335 Zornitza Stark Gene: znf335 has been classified as Green List (High Evidence).
Fetal anomalies v1.3 ZNF335 Zornitza Stark Marked gene: ZNF335 as ready
Fetal anomalies v1.3 ZNF335 Zornitza Stark Gene: znf335 has been classified as Green List (High Evidence).
Fetal anomalies v1.3 ZNF335 Zornitza Stark Classified gene: ZNF335 as Green List (high evidence)
Fetal anomalies v1.3 ZNF335 Zornitza Stark Gene: znf335 has been classified as Green List (High Evidence).
Fetal anomalies v1.2 ZNF335 Zornitza Stark gene: ZNF335 was added
gene: ZNF335 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: ZNF335 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF335 were set to 23178126; 27540107; 29652087; 34982360
Phenotypes for gene: ZNF335 were set to Microcephaly 10, primary, autosomal recessive (MIM#615095)
Review for gene: ZNF335 was set to GREEN
Added comment: Microcephaly is generally primary, including reports of -9SD at birth.
Sources: Expert Review
Mendeliome v0.11145 ZNF335 Zornitza Stark Phenotypes for gene: ZNF335 were changed from to Microcephaly 10, primary, autosomal recessive (MIM#615095)
Mendeliome v0.11144 ZNF335 Zornitza Stark Publications for gene: ZNF335 were set to
Mendeliome v0.11143 ZNF335 Zornitza Stark Mode of inheritance for gene: ZNF335 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11142 ZNF335 Zornitza Stark reviewed gene: ZNF335: Rating: GREEN; Mode of pathogenicity: None; Publications: 23178126, 27540107, 29652087; Phenotypes: Microcephaly 10, primary, autosomal recessive (MIM#615095); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11142 ZMYND11 Zornitza Stark Marked gene: ZMYND11 as ready
Mendeliome v0.11142 ZMYND11 Zornitza Stark Gene: zmynd11 has been classified as Green List (High Evidence).
Mendeliome v0.11142 ZMYND11 Zornitza Stark Phenotypes for gene: ZMYND11 were changed from to Mental retardation, autosomal dominant 30, MIM# 616083
Mendeliome v0.11141 ZMYND11 Zornitza Stark Publications for gene: ZMYND11 were set to
Mendeliome v0.11140 ZMYND11 Zornitza Stark Mode of inheritance for gene: ZMYND11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11139 ZMYND11 Zornitza Stark reviewed gene: ZMYND11: Rating: GREEN; Mode of pathogenicity: None; Publications: 32097528, 34216016; Phenotypes: Mental retardation, autosomal dominant 30 MIM# 616083; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.199 ZFPM2 Zornitza Stark Marked gene: ZFPM2 as ready
Congenital Heart Defect v0.199 ZFPM2 Zornitza Stark Gene: zfpm2 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.199 ZFPM2 Zornitza Stark Phenotypes for gene: ZFPM2 were changed from to Tetralogy of Fallot, MIM# 187500
Congenital Heart Defect v0.198 ZFPM2 Zornitza Stark Publications for gene: ZFPM2 were set to
Congenital Heart Defect v0.197 ZFPM2 Zornitza Stark Mode of inheritance for gene: ZFPM2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.196 ZFPM2 Zornitza Stark Classified gene: ZFPM2 as Amber List (moderate evidence)
Congenital Heart Defect v0.196 ZFPM2 Zornitza Stark Gene: zfpm2 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.195 ZFPM2 Zornitza Stark reviewed gene: ZFPM2: Rating: AMBER; Mode of pathogenicity: None; Publications: 21919901, 24469719, 26959486; Phenotypes: Tetralogy of Fallot, MIM# 187500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11139 ZFPM2 Zornitza Stark Marked gene: ZFPM2 as ready
Mendeliome v0.11139 ZFPM2 Zornitza Stark Gene: zfpm2 has been classified as Green List (High Evidence).
Mendeliome v0.11139 ZFPM2 Zornitza Stark Phenotypes for gene: ZFPM2 were changed from to Diaphragmatic hernia 3, MIM# 610187; 46XY sex reversal 9 (MIM#616067); Tetralogy of Fallot, MIM# 187500
Mendeliome v0.11138 ZFPM2 Zornitza Stark Publications for gene: ZFPM2 were set to
Mendeliome v0.11137 ZFPM2 Zornitza Stark Mode of inheritance for gene: ZFPM2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11136 ZFPM2 Zornitza Stark reviewed gene: ZFPM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 16103912, 17568391, 24702427, 24549039, 27899157, 31962012, 12223418, 20807224, 21919901, 24469719, 26959486; Phenotypes: Diaphragmatic hernia 3, MIM# 610187, 46XY sex reversal 9 (MIM#616067), Tetralogy of Fallot, MIM# 187500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.1 MAN2C1 Zornitza Stark Phenotypes for gene: MAN2C1 were changed from MAN2C1-related neurodevelopmental disorder MONDO:0700092 to Congenital disorder of deglycosylation 2, MIM# 619775
Fetal anomalies v1.0 MAN2C1 Zornitza Stark reviewed gene: MAN2C1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of deglycosylation 2, MIM# 619775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4535 MAN2C1 Zornitza Stark Marked gene: MAN2C1 as ready
Intellectual disability syndromic and non-syndromic v0.4535 MAN2C1 Zornitza Stark Gene: man2c1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4535 MAN2C1 Zornitza Stark Phenotypes for gene: MAN2C1 were changed from neurodevelopmental disorder MONDO:0700092 MAN2C1-related to Congenital disorder of deglycosylation 2, MIM# 619775
Intellectual disability syndromic and non-syndromic v0.4534 MAN2C1 Zornitza Stark Classified gene: MAN2C1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4534 MAN2C1 Zornitza Stark Gene: man2c1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4533 MAN2C1 Zornitza Stark reviewed gene: MAN2C1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of deglycosylation 2, MIM# 619775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11136 MAN2C1 Zornitza Stark Phenotypes for gene: MAN2C1 were changed from neurodevelopmental disorder, MAN2C1-related, MONDO:0700092 to Congenital disorder of deglycosylation 2, MIM# 619775
Mendeliome v0.11135 MAN2C1 Zornitza Stark reviewed gene: MAN2C1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of deglycosylation 2, MIM# 619775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v1.46 MAN2C1 Zornitza Stark Phenotypes for gene: MAN2C1 were changed from neurodevelopmental disorder MONDO:0700092 MAN2C1-related to Congenital disorder of deglycosylation 2, MIM# 619775
Cerebellar and Pontocerebellar Hypoplasia v1.45 MAN2C1 Zornitza Stark reviewed gene: MAN2C1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of deglycosylation 2, MIM# 619775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polymicrogyria and Schizencephaly v0.172 MAN2C1 Zornitza Stark Phenotypes for gene: MAN2C1 were changed from neurodevelopmental disorder, MAN2C1-related, MONDO:0700092 to Congenital disorder of deglycosylation 2, MIM# 619775
Polymicrogyria and Schizencephaly v0.171 MAN2C1 Zornitza Stark reviewed gene: MAN2C1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of deglycosylation 2, MIM# 619775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
IBMDx study v0.20 RPA1 Zornitza Stark Marked gene: RPA1 as ready
IBMDx study v0.20 RPA1 Zornitza Stark Gene: rpa1 has been classified as Green List (High Evidence).
IBMDx study v0.20 RPA1 Zornitza Stark Phenotypes for gene: RPA1 were changed from New TBD gene ASH 2020 St Judes to Pulmonary fibrosis and/or bone marrow failure, telomere-related, 6, MIM# 619767; Bone marrow failure; T- and B-cell lymphopaenia; pulmonary fibrosis; skin manifestations; short telomeres
IBMDx study v0.19 RPA1 Zornitza Stark Publications for gene: RPA1 were set to
IBMDx study v0.18 RPA1 Zornitza Stark Mode of pathogenicity for gene: RPA1 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
IBMDx study v0.17 RPA1 Zornitza Stark Mode of inheritance for gene: RPA1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
IBMDx study v0.16 RPA1 Zornitza Stark edited their review of gene: RPA1: Changed phenotypes: Pulmonary fibrosis and/or bone marrow failure, telomere-related, 6, MIM# 619767, Bone marrow failure, T- and B-cell lymphopaenia, pulmonary fibrosis, skin manifestations, short telomeres
Pulmonary Fibrosis_Interstitial Lung Disease v0.42 RPA1 Zornitza Stark Phenotypes for gene: RPA1 were changed from Bone marrow failure; T- and B-cell lymphopaenia; pulmonary fibrosis; skin manifestations; short telomeres to Pulmonary fibrosis and/or bone marrow failure, telomere-related, 6, MIM# 619767; Bone marrow failure; T- and B-cell lymphopaenia; pulmonary fibrosis; skin manifestations; short telomeres
Pulmonary Fibrosis_Interstitial Lung Disease v0.41 RPA1 Zornitza Stark edited their review of gene: RPA1: Changed phenotypes: Pulmonary fibrosis and/or bone marrow failure, telomere-related, 6, MIM# 619767, Bone marrow failure, T- and B-cell lymphopaenia, pulmonary fibrosis, skin manifestations, short telomeres
Mendeliome v0.11135 RPA1 Zornitza Stark Phenotypes for gene: RPA1 were changed from Bone marrow failure; T- and B-cell lymphopaenia; pulmonary fibrosis; skin manifestations; short telomeres to Pulmonary fibrosis and/or bone marrow failure, telomere-related, 6, MIM# 619767; Bone marrow failure; T- and B-cell lymphopaenia; pulmonary fibrosis; skin manifestations; short telomeres
Mendeliome v0.11134 RPA1 Zornitza Stark edited their review of gene: RPA1: Changed phenotypes: Pulmonary fibrosis and/or bone marrow failure, telomere-related, 6, MIM# 619767, Bone marrow failure, T- and B-cell lymphopaenia, pulmonary fibrosis, skin manifestations, short telomeres
Bone Marrow Failure v1.10 RPA1 Zornitza Stark Phenotypes for gene: RPA1 were changed from Bone marrow failure; T- and B-cell lymphopaenia; pulmonary fibrosis; skin manifestations; short telomeres to Pulmonary fibrosis and/or bone marrow failure, telomere-related, 6, MIM# 619767; Bone marrow failure; T- and B-cell lymphopaenia; pulmonary fibrosis; skin manifestations; short telomeres
Bone Marrow Failure v1.9 RPA1 Zornitza Stark edited their review of gene: RPA1: Changed phenotypes: Pulmonary fibrosis and/or bone marrow failure, telomere-related, 6, MIM# 619767, Bone marrow failure, T- and B-cell lymphopaenia, pulmonary fibrosis, skin manifestations, short telomeres
Mendeliome v0.11134 OPCML Zornitza Stark Marked gene: OPCML as ready
Mendeliome v0.11134 OPCML Zornitza Stark Gene: opcml has been classified as Red List (Low Evidence).
Mendeliome v0.11134 OPCML Zornitza Stark Phenotypes for gene: OPCML were changed from to Ovarian cancer, somatic, MIM#167000
Mendeliome v0.11133 OPCML Zornitza Stark Classified gene: OPCML as Red List (low evidence)
Mendeliome v0.11133 OPCML Zornitza Stark Gene: opcml has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.4533 NFE2L1 Zornitza Stark Marked gene: NFE2L1 as ready
Intellectual disability syndromic and non-syndromic v0.4533 NFE2L1 Zornitza Stark Gene: nfe2l1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.4533 NFE2L1 Zornitza Stark gene: NFE2L1 was added
gene: NFE2L1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: NFE2L1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NFE2L1 were set to 35112409
Phenotypes for gene: NFE2L1 were set to Syndromic disease, MONDO:0002254
Review for gene: NFE2L1 was set to RED
Added comment: A single patient with developmental delay, hypotonia, hypospadias, bifid scrotum, and failure to thrive, with a heterozygous nonsense variant in the last exon. In vitro functional assays suggest a dominant-negative effect.
Sources: Literature
Stickler Syndrome v1.3 COL9A3 Zornitza Stark changed review comment from: Note mono-allelic variants have been associated with isolated deafness and retinal phenotypes which overlap with Stickler syndrome.; to: Note mono-allelic variants have been associated with isolated deafness and retinal phenotypes which overlap with Stickler syndrome.

However, of the two families with isolated retinal phenotype, one of the variants reported has a high population frequency, not compatible with a monogenic disorder, PMID 33633367.
Vitreoretinopathy v1.3 COL9A3 Zornitza Stark Classified gene: COL9A3 as Amber List (moderate evidence)
Vitreoretinopathy v1.3 COL9A3 Zornitza Stark Gene: col9a3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11132 OPCML Naomi Baker reviewed gene: OPCML: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ovarian cancer, somatic, MIM#167000; Mode of inheritance: Other
Mendeliome v0.11132 NFE2L1 Bryony Thompson Marked gene: NFE2L1 as ready
Mendeliome v0.11132 NFE2L1 Bryony Thompson Gene: nfe2l1 has been classified as Red List (Low Evidence).
Mendeliome v0.11132 NFE2L1 Bryony Thompson gene: NFE2L1 was added
gene: NFE2L1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NFE2L1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NFE2L1 were set to 35112409
Phenotypes for gene: NFE2L1 were set to Syndromic disease, MONDO:0002254
Review for gene: NFE2L1 was set to RED
Added comment: A single patient with developmental delay, hypotonia, hypospadias, bifid scrotum, and failure to thrive, with a heterozygous nonsense variant in the last exon. In vitro functional assays suggest a dominant-negative effect.
Sources: Literature
Vitreoretinopathy v1.2 COL9A3 Ain Roesley changed review comment from: In family 2 with missense Gly130Ser, there is 228 hets 0 homs in gnomAD v2.

This leaves 1 family with the splice variant which is absent in gnomAD, cDNA studies to prove a splice defect and segregation in 14 affecteds across 2 generations; to: In family 2 with missense Gly130Ser, there is 228 hets 0 homs in gnomAD v2.

This leaves 1 family with the splice variant which is absent in gnomAD, cDNA studies to prove a splice defect and segregation in 11 affecteds (genotyped) across 2 generations
Mendeliome v0.11131 ZFP57 Zornitza Stark Marked gene: ZFP57 as ready
Mendeliome v0.11131 ZFP57 Zornitza Stark Gene: zfp57 has been classified as Green List (High Evidence).
Mendeliome v0.11131 ZFP57 Zornitza Stark Phenotypes for gene: ZFP57 were changed from to IUGR; Diabetes mellitus, transient neonatal 1 OMIM:601410; Multi Locus Imprinting Disturbance; diabetes mellitus, transient neonatal, 1, MONDO:0011073
Mendeliome v0.11130 ZFP57 Zornitza Stark Publications for gene: ZFP57 were set to
Mendeliome v0.11129 ZFP57 Zornitza Stark Mode of inheritance for gene: ZFP57 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11128 ZFP57 Zornitza Stark reviewed gene: ZFP57: Rating: GREEN; Mode of pathogenicity: None; Publications: 18622393, 27075368, 23150280, 30315371, 31399135, 33053156; Phenotypes: IUGR, Diabetes mellitus, transient neonatal 1 OMIM:601410, Multi Locus Imprinting Disturbance, diabetes mellitus, transient neonatal, 1MONDO:0011073; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11128 XYLT2 Zornitza Stark Marked gene: XYLT2 as ready
Mendeliome v0.11128 XYLT2 Zornitza Stark Gene: xylt2 has been classified as Green List (High Evidence).
Mendeliome v0.11128 XYLT2 Zornitza Stark Phenotypes for gene: XYLT2 were changed from to Spondyloocular syndrome MIM# 605822
Mendeliome v0.11127 XYLT2 Zornitza Stark Publications for gene: XYLT2 were set to
Mendeliome v0.11126 XYLT2 Zornitza Stark Mode of inheritance for gene: XYLT2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11125 XYLT2 Zornitza Stark reviewed gene: XYLT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26027496, 26987875, 30891060, 28484880; Phenotypes: Spondyloocular syndrome MIM# 605822; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11125 XRCC3 Zornitza Stark Marked gene: XRCC3 as ready
Mendeliome v0.11125 XRCC3 Zornitza Stark Gene: xrcc3 has been classified as Red List (Low Evidence).
Mendeliome v0.11125 XRCC3 Zornitza Stark Classified gene: XRCC3 as Red List (low evidence)
Mendeliome v0.11125 XRCC3 Zornitza Stark Gene: xrcc3 has been classified as Red List (Low Evidence).
Mendeliome v0.11124 XRCC3 Zornitza Stark reviewed gene: XRCC3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Disorders of immune dysregulation v0.109 XIAP Zornitza Stark Phenotypes for gene: XIAP were changed from to Lymphoproliferative syndrome, X-linked, 2, MIM# 300635
Disorders of immune dysregulation v0.108 XIAP Zornitza Stark Publications for gene: XIAP were set to 22228567; 25943627
Disorders of immune dysregulation v0.107 XIAP Zornitza Stark Publications for gene: XIAP were set to
Disorders of immune dysregulation v0.107 XIAP Zornitza Stark Mode of inheritance for gene: XIAP was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Predominantly Antibody Deficiency v0.98 XIAP Zornitza Stark Marked gene: XIAP as ready
Predominantly Antibody Deficiency v0.98 XIAP Zornitza Stark Gene: xiap has been classified as Green List (High Evidence).
Predominantly Antibody Deficiency v0.98 XIAP Zornitza Stark Phenotypes for gene: XIAP were changed from to Lymphoproliferative syndrome, X-linked, 2, MIM# 300635
Mendeliome v0.11124 XIAP Zornitza Stark Marked gene: XIAP as ready
Mendeliome v0.11124 XIAP Zornitza Stark Gene: xiap has been classified as Green List (High Evidence).
Predominantly Antibody Deficiency v0.97 XIAP Zornitza Stark Publications for gene: XIAP were set to
Disorders of immune dysregulation v0.106 XIAP Zornitza Stark reviewed gene: XIAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 22228567, 25943627; Phenotypes: Lymphoproliferative syndrome, X-linked, 2, MIM# 300635; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Predominantly Antibody Deficiency v0.96 XIAP Zornitza Stark Mode of inheritance for gene: XIAP was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Predominantly Antibody Deficiency v0.95 XIAP Zornitza Stark reviewed gene: XIAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 22228567, 25943627; Phenotypes: Lymphoproliferative syndrome, X-linked, 2, MIM# 300635; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.11124 XIAP Zornitza Stark Phenotypes for gene: XIAP were changed from to Lymphoproliferative syndrome, X-linked, 2, MIM# 300635
Mendeliome v0.11123 XIAP Zornitza Stark Publications for gene: XIAP were set to
Mendeliome v0.11122 XIAP Zornitza Stark Mode of inheritance for gene: XIAP was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.11121 XIAP Zornitza Stark reviewed gene: XIAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 22228567, 25943627; Phenotypes: Lymphoproliferative syndrome, X-linked, 2, MIM# 300635; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.11121 XG Zornitza Stark Marked gene: XG as ready
Mendeliome v0.11121 XG Zornitza Stark Gene: xg has been classified as Red List (Low Evidence).
Mendeliome v0.11121 XG Zornitza Stark Classified gene: XG as Red List (low evidence)
Mendeliome v0.11121 XG Zornitza Stark Gene: xg has been classified as Red List (Low Evidence).
Mendeliome v0.11120 XG Zornitza Stark reviewed gene: XG: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.4532 QDPR Zornitza Stark Marked gene: QDPR as ready
Intellectual disability syndromic and non-syndromic v0.4532 QDPR Zornitza Stark Gene: qdpr has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4532 QDPR Zornitza Stark Phenotypes for gene: QDPR were changed from to Hyperphenylalaninemia, BH4-deficient, C, MIM# 261630
Intellectual disability syndromic and non-syndromic v0.4531 QDPR Zornitza Stark Publications for gene: QDPR were set to
Intellectual disability syndromic and non-syndromic v0.4530 QDPR Zornitza Stark Mode of inheritance for gene: QDPR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4529 QDPR Zornitza Stark reviewed gene: QDPR: Rating: GREEN; Mode of pathogenicity: None; Publications: 11153907; Phenotypes: Hyperphenylalaninemia, BH4-deficient, C, MIM# 261630; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11120 QDPR Zornitza Stark Phenotypes for gene: QDPR were changed from to Hyperphenylalaninemia, BH4-deficient, C, MIM# 261630
Mendeliome v0.11119 QDPR Zornitza Stark Publications for gene: QDPR were set to
Mendeliome v0.11118 QDPR Zornitza Stark Mode of inheritance for gene: QDPR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11117 QDPR Zornitza Stark reviewed gene: QDPR: Rating: GREEN; Mode of pathogenicity: None; Publications: 11153907; Phenotypes: Hyperphenylalaninemia, BH4-deficient, C, MIM# 261630; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11117 RRM2B Zornitza Stark Phenotypes for gene: RRM2B were changed from Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy) MIM#612075; Mitochondrial DNA depletion syndrome 8B (MNGIE type) MIM#612075 to Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy) MIM#612075; Mitochondrial DNA depletion syndrome 8B (MNGIE type) MIM#612075; Rod-cone dystrophy, sensorineural deafness, and Fanconi-type renal dysfunction, MIM# 268315
Mendeliome v0.11116 RRM2B Zornitza Stark Publications for gene: RRM2B were set to 24741716
Mendeliome v0.11115 RRM2B Zornitza Stark reviewed gene: RRM2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 32827185; Phenotypes: Rod-cone dystrophy, sensorineural deafness, and Fanconi-type renal dysfunction, MIM# 268315; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11115 OPDM4 Bryony Thompson Marked STR: OPDM4 as ready
Mendeliome v0.11115 OPDM4 Bryony Thompson Str: opdm4 has been classified as Green List (High Evidence).
Mendeliome v0.11115 OPDM4 Bryony Thompson Classified STR: OPDM4 as Green List (high evidence)
Mendeliome v0.11115 OPDM4 Bryony Thompson Str: opdm4 has been classified as Green List (High Evidence).
Mendeliome v0.11114 OPDM4 Bryony Thompson STR: OPDM4 was added
STR: OPDM4 was added to Mendeliome. Sources: Literature
Mode of inheritance for STR: OPDM4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: OPDM4 were set to 35148830
Phenotypes for STR: OPDM4 were set to Oculopharyngodistal myopathy MONDO:0025193
Review for STR: OPDM4 was set to GREEN
STR: OPDM4 was marked as clinically relevant
Added comment: 5'UTR repeat upstream of RILPL1. Analyses suggest that toxic RNA gain-of-function is the mechanism of disease for the repeat expansion. Distribution of CGG repeat units in RILPL1 ranged from 9 to 16 among 200 normal controls. The size of the CGG repeat ranged from 139 to 197 (169.91 ± 21.82) repeats in 11 unrelated individuals with OPDM. Segregation evidence from 1 family, with 2 affected individuals with the repeat expansion and 1 individual with essential tremor but not OPDM and 86 repeats (intermediate).
Sources: Literature
Repeat Disorders v0.150 OPDM4 Bryony Thompson Marked STR: OPDM4 as ready
Repeat Disorders v0.150 OPDM4 Bryony Thompson Str: opdm4 has been classified as Green List (High Evidence).
Repeat Disorders v0.150 OPDM4 Bryony Thompson Classified STR: OPDM4 as Green List (high evidence)
Repeat Disorders v0.150 OPDM4 Bryony Thompson Str: opdm4 has been classified as Green List (High Evidence).
Repeat Disorders v0.149 OPDM4 Bryony Thompson STR: OPDM4 was added
STR: OPDM4 was added to Repeat Disorders. Sources: Literature
Mode of inheritance for STR: OPDM4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: OPDM4 were set to 35148830
Phenotypes for STR: OPDM4 were set to Oculopharyngodistal myopathy MONDO:0025193
Review for STR: OPDM4 was set to GREEN
STR: OPDM4 was marked as clinically relevant
Added comment: 5'UTR repeat upstream of RILPL1. Analyses suggest that toxic RNA gain-of-function is the mechanism of disease for the repeat expansion.
Distribution of CGG repeat units in RILPL1 ranged from 9 to 16 among 200 normal controls. The size of the CGG repeat ranged from 139 to 197 (169.91 ± 21.82) repeats in 11 unrelated individuals with OPDM. Segregation evidence from 1 family, with 2 affected individuals with the repeat expansion and 1 individual with essential tremor but not OPDM and 86 repeats (intermediate).
Sources: Literature
Fetal anomalies v1.0 Zornitza Stark promoted panel to version 1.0
Fetal anomalies v0.4732 OXR1 Zornitza Stark Marked gene: OXR1 as ready
Fetal anomalies v0.4732 OXR1 Zornitza Stark Gene: oxr1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4732 OXR1 Zornitza Stark Classified gene: OXR1 as Amber List (moderate evidence)
Fetal anomalies v0.4732 OXR1 Zornitza Stark Gene: oxr1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4731 OXR1 Zornitza Stark reviewed gene: OXR1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebellar hypoplasia/atrophy, epilepsy, and global developmental delay - MIM#213000; Mode of inheritance: None
Fetal anomalies v0.4731 MED27 Zornitza Stark Marked gene: MED27 as ready
Fetal anomalies v0.4731 MED27 Zornitza Stark Gene: med27 has been classified as Green List (High Evidence).
Fetal anomalies v0.4731 MED27 Zornitza Stark Classified gene: MED27 as Green List (high evidence)
Fetal anomalies v0.4731 MED27 Zornitza Stark Gene: med27 has been classified as Green List (High Evidence).
Fetal anomalies v0.4730 EXOSC9 Zornitza Stark Marked gene: EXOSC9 as ready
Fetal anomalies v0.4730 EXOSC9 Zornitza Stark Gene: exosc9 has been classified as Green List (High Evidence).
Fetal anomalies v0.4730 EXOSC9 Zornitza Stark Classified gene: EXOSC9 as Green List (high evidence)
Fetal anomalies v0.4730 EXOSC9 Zornitza Stark Gene: exosc9 has been classified as Green List (High Evidence).
Fetal anomalies v0.4729 OXR1 Krithika Murali gene: OXR1 was added
gene: OXR1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: OXR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OXR1 were set to PMID: 31785787
Phenotypes for gene: OXR1 were set to Cerebellar hypoplasia/atrophy, epilepsy, and global developmental delay - MIM#213000
Review for gene: OXR1 was set to GREEN
Added comment: Early-onset condition associated with cerebellar atrophy and severe global developmental delay. Limited antenatal information provided but affected individuals were much older at the time of formal diagnosis PMID: 31785787, antenatal detection may be possible.

---
5 individuals from 3 unrelated families reported with bi-allelic variants in this gene. Presentation was in early childhood with hypotonia, global developmental delay, delayed walking at about age 3 years, and severely impaired intellectual development with profound speech delay or even absent language. All also developed epilepsy between 7 and 10 years of age, but the seizures were controlled by medication in most. Subtle nonspecific dysmorphic features included poor overall growth, large forehead, tall face, mild hypertelorism, joint hyperlaxity, and long fingers and toes. Brain imaging in all 5 individuals showed cerebellar atrophy and dysplasia. Additional cerebellar features, such as tremor, ataxia, and nystagmus, were not noted in these individuals.
Sources: Literature
Fetal anomalies v0.4729 MED27 Krithika Murali gene: MED27 was added
gene: MED27 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MED27 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MED27 were set to 33443317
Phenotypes for gene: MED27 were set to Neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia - MIM#619286
Review for gene: MED27 was set to GREEN
Added comment: Severe neurodevelopmental disorder with onset in infancy associated with multiple, significant brain anomalies which may be detectable antenatally (although antenatal phenotype not reported in published cases)
Sources: Literature
Fetal anomalies v0.4729 EXOSC9 Krithika Murali gene: EXOSC9 was added
gene: EXOSC9 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: EXOSC9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOSC9 were set to 33040083; 30690203; 29727687
Phenotypes for gene: EXOSC9 were set to Pontocerebellar hypoplasia, type 1D - MIM#618065
Review for gene: EXOSC9 was set to GREEN
Added comment: Multiple antenatal features reported including IUGR, reduced fetal movements, oligohydramnios, congenital fractures and contractures.
Sources: Literature
Fetal anomalies v0.4729 EXOSC8 Zornitza Stark Marked gene: EXOSC8 as ready
Fetal anomalies v0.4729 EXOSC8 Zornitza Stark Gene: exosc8 has been classified as Green List (High Evidence).
Fetal anomalies v0.4729 EXOSC8 Zornitza Stark Classified gene: EXOSC8 as Green List (high evidence)
Fetal anomalies v0.4729 EXOSC8 Zornitza Stark Gene: exosc8 has been classified as Green List (High Evidence).
Fetal anomalies v0.4728 EXOSC5 Zornitza Stark Marked gene: EXOSC5 as ready
Fetal anomalies v0.4728 EXOSC5 Zornitza Stark Gene: exosc5 has been classified as Green List (High Evidence).
Fetal anomalies v0.4728 EXOSC5 Zornitza Stark Classified gene: EXOSC5 as Green List (high evidence)
Fetal anomalies v0.4728 EXOSC5 Zornitza Stark Gene: exosc5 has been classified as Green List (High Evidence).
Fetal anomalies v0.4727 CWF19L1 Zornitza Stark Marked gene: CWF19L1 as ready
Fetal anomalies v0.4727 CWF19L1 Zornitza Stark Gene: cwf19l1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4727 CWF19L1 Zornitza Stark Classified gene: CWF19L1 as Green List (high evidence)
Fetal anomalies v0.4727 CWF19L1 Zornitza Stark Gene: cwf19l1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4726 RBP4 Zornitza Stark Marked gene: RBP4 as ready
Fetal anomalies v0.4726 RBP4 Zornitza Stark Gene: rbp4 has been classified as Green List (High Evidence).
Fetal anomalies v0.4726 RBP4 Zornitza Stark Classified gene: RBP4 as Green List (high evidence)
Fetal anomalies v0.4726 RBP4 Zornitza Stark Gene: rbp4 has been classified as Green List (High Evidence).
Fetal anomalies v0.4725 RBP4 Zornitza Stark gene: RBP4 was added
gene: RBP4 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: RBP4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RBP4 were set to 25910211; 29178648
Phenotypes for gene: RBP4 were set to Microphthalmia, isolated, with coloboma 10 MIM#616428
Review for gene: RBP4 was set to GREEN
Added comment: At least 3 unrelated microphthalmia, anophthalmia and coloboma families and supporting functional assays. Study established an uncharacterized mode of maternal inheritance, distinct from imprinting and oocyte-derived mRNA.
Sources: Expert Review
Fetal anomalies v0.4724 PRR12 Zornitza Stark Marked gene: PRR12 as ready
Fetal anomalies v0.4724 PRR12 Zornitza Stark Gene: prr12 has been classified as Green List (High Evidence).
Fetal anomalies v0.4724 PRR12 Zornitza Stark Classified gene: PRR12 as Green List (high evidence)
Fetal anomalies v0.4724 PRR12 Zornitza Stark Gene: prr12 has been classified as Green List (High Evidence).
Fetal anomalies v0.4723 PRR12 Zornitza Stark gene: PRR12 was added
gene: PRR12 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: PRR12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRR12 were set to 33314030; 29556724
Phenotypes for gene: PRR12 were set to Neuroocular syndrome, MIM#619539; Complex microphthalmia
Review for gene: PRR12 was set to GREEN
Added comment: PMID 33314030: Four unrelated families reported with unilateral or bilateral microphthalmia +/- Peters anomaly. In addition, 3 unrelated families reported with more complex phenotype including ID in PMID 29556724.
Sources: Expert Review
Fetal anomalies v0.4722 EXOSC8 Krithika Murali changed review comment from: Severe autosomal recessive neurodegenerative disorder. PMID 24989451 report polyhydramnios, vermis hypoplasia, mega cisterna magna and corpus callosum anomalies in affectd individuals
Sources: Literature; to: Severe autosomal recessive neurodegenerative disorder. PMID 24989451 (more info in supplementary material) report polyhydramnios, vermis hypoplasia, mega cisterna magna and corpus callosum anomalies in affectd individuals
Sources: Literature
Fetal anomalies v0.4722 EXOSC8 Krithika Murali gene: EXOSC8 was added
gene: EXOSC8 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: EXOSC8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOSC8 were set to 34210538; 24989451
Phenotypes for gene: EXOSC8 were set to Pontocerebellar hypoplasia, type 1C - MIM#616081
Review for gene: EXOSC8 was set to GREEN
Added comment: Severe autosomal recessive neurodegenerative disorder. PMID 24989451 report polyhydramnios, vermis hypoplasia, mega cisterna magna and corpus callosum anomalies in affectd individuals
Sources: Literature
Fetal anomalies v0.4722 MAB21L1 Zornitza Stark Marked gene: MAB21L1 as ready
Fetal anomalies v0.4722 MAB21L1 Zornitza Stark Gene: mab21l1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4722 MAB21L1 Zornitza Stark Classified gene: MAB21L1 as Green List (high evidence)
Fetal anomalies v0.4722 MAB21L1 Zornitza Stark Gene: mab21l1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4721 MAB21L1 Zornitza Stark gene: MAB21L1 was added
gene: MAB21L1 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: MAB21L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAB21L1 were set to 30487245
Phenotypes for gene: MAB21L1 were set to Cerebellar, ocular, craniofacial, and genital syndrome OMIM#618479
Review for gene: MAB21L1 was set to GREEN
Added comment: Pontocerebellar hypoplasia, Dandy-Walker malformation, microcephaly reported.
Sources: Expert Review
Fetal anomalies v0.4720 FBXW11 Zornitza Stark Marked gene: FBXW11 as ready
Fetal anomalies v0.4720 FBXW11 Zornitza Stark Gene: fbxw11 has been classified as Green List (High Evidence).
Fetal anomalies v0.4720 FBXW11 Zornitza Stark Classified gene: FBXW11 as Green List (high evidence)
Fetal anomalies v0.4720 FBXW11 Zornitza Stark Gene: fbxw11 has been classified as Green List (High Evidence).
Fetal anomalies v0.4719 FBXW11 Zornitza Stark changed review comment from: 7 unrelated individuals; structural brain, eye and limb anomalies.
Sources: Expert Review; to: 7 unrelated individuals; structural brain, craniofacial, eye and limb anomalies.
Sources: Expert Review
Fetal anomalies v0.4719 FBXW11 Zornitza Stark gene: FBXW11 was added
gene: FBXW11 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: FBXW11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FBXW11 were set to Neurodevelopmental, eye, jaw, and digital syndrome (NDEJD), MIM#618914
Review for gene: FBXW11 was set to GREEN
Added comment: 7 unrelated individuals; structural brain, eye and limb anomalies.
Sources: Expert Review
Fetal anomalies v0.4718 EXOSC5 Krithika Murali gene: EXOSC5 was added
gene: EXOSC5 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: EXOSC5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOSC5 were set to 32504085; 29302074
Phenotypes for gene: EXOSC5 were set to Cerebellar ataxia, brain abnormalities, and cardiac conduction defects - MIM#619576
Review for gene: EXOSC5 was set to GREEN
Added comment: Associated with congenital anomalies
Sources: Literature
Fetal anomalies v0.4718 CAPN15 Zornitza Stark Marked gene: CAPN15 as ready
Fetal anomalies v0.4718 CAPN15 Zornitza Stark Gene: capn15 has been classified as Green List (High Evidence).
Fetal anomalies v0.4718 CAPN15 Zornitza Stark Classified gene: CAPN15 as Green List (high evidence)
Fetal anomalies v0.4718 CAPN15 Zornitza Stark Gene: capn15 has been classified as Green List (High Evidence).
Fetal anomalies v0.4717 CAPN15 Zornitza Stark gene: CAPN15 was added
gene: CAPN15 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: CAPN15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAPN15 were set to 32885237
Phenotypes for gene: CAPN15 were set to Oculogastrointestinal neurodevelopmental syndrome, MIM# 619318; microphthalmia HP:0000568; coloboma HP:0000589
Review for gene: CAPN15 was set to GREEN
Added comment: PMID: 32885237 - Zha et al 2020 - report 5 individuals with microphthalmia and/or coloboma from 4 independent families who, through WES, were identified as carrying homozygous or compound heterozygous missense variants in CAPN15 that are predicted to be damanging. the variants segregated with the disease in all 4 families, with parents being unaffected heterozygous carriers. Several individuals had additional phenotypes including growth deficits (2 families), developmental delay (2 families) and hearing loss (2 families). Capn15 knockout mice showed similar severe developmental eye defects, including anophthalmia, microphthalmia and cataract, and diminished growth.
Sources: Expert Review
Fetal anomalies v0.4716 C16orf62 Zornitza Stark Marked gene: C16orf62 as ready
Fetal anomalies v0.4716 C16orf62 Zornitza Stark Gene: c16orf62 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4716 C16orf62 Zornitza Stark Classified gene: C16orf62 as Amber List (moderate evidence)
Fetal anomalies v0.4716 C16orf62 Zornitza Stark Gene: c16orf62 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4715 C16orf62 Zornitza Stark changed review comment from: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475;31712251).

Microphthalmia and multiple other anomalies.
Sources: Expert Review; to: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impaired autophagy and VPS35L knockout mouse resulted in early embryonic lethality (PMID 25434475;31712251).

Microphthalmia and multiple other anomalies.
Sources: Expert Review
Fetal anomalies v0.4715 C16orf62 Zornitza Stark gene: C16orf62 was added
gene: C16orf62 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: C16orf62 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C16orf62 were set to 25434475; 31712251
Phenotypes for gene: C16orf62 were set to Ritscher-Schinzel syndrome-3 (RTSC3), MIM#619135
Review for gene: C16orf62 was set to AMBER
Added comment: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475;31712251).

Microphthalmia and multiple other anomalies.
Sources: Expert Review
Fetal anomalies v0.4714 CWF19L1 Krithika Murali gene: CWF19L1 was added
gene: CWF19L1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CWF19L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CWF19L1 were set to 27016154
Phenotypes for gene: CWF19L1 were set to Spinocerebellar ataxia, autosomal recessive 17 - MIM#616127
Review for gene: CWF19L1 was set to GREEN
Added comment: Fetal phenotype also described by 27016154 - MTOP at 22 weeks of gestation of an affected fetus due to small cerebellum and agenesis of corpus callosum. Postmortem examination showed unilateral hexadactyly and vertebral malformations.
Sources: Literature
Fetal anomalies v0.4714 TMEM218 Zornitza Stark Marked gene: TMEM218 as ready
Fetal anomalies v0.4714 TMEM218 Zornitza Stark Gene: tmem218 has been classified as Green List (High Evidence).
Fetal anomalies v0.4714 TMEM218 Zornitza Stark Classified gene: TMEM218 as Green List (high evidence)
Fetal anomalies v0.4714 TMEM218 Zornitza Stark Gene: tmem218 has been classified as Green List (High Evidence).
Fetal anomalies v0.4713 NID1 Zornitza Stark Marked gene: NID1 as ready
Fetal anomalies v0.4713 NID1 Zornitza Stark Gene: nid1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4713 NID1 Zornitza Stark Classified gene: NID1 as Green List (high evidence)
Fetal anomalies v0.4713 NID1 Zornitza Stark Gene: nid1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4712 MTX2 Zornitza Stark Marked gene: MTX2 as ready
Fetal anomalies v0.4712 MTX2 Zornitza Stark Gene: mtx2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4712 MTX2 Zornitza Stark Classified gene: MTX2 as Green List (high evidence)
Fetal anomalies v0.4712 MTX2 Zornitza Stark Gene: mtx2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4711 KIAA0556 Zornitza Stark Marked gene: KIAA0556 as ready
Fetal anomalies v0.4711 KIAA0556 Zornitza Stark Gene: kiaa0556 has been classified as Green List (High Evidence).
Fetal anomalies v0.4711 KIAA0556 Zornitza Stark Classified gene: KIAA0556 as Green List (high evidence)
Fetal anomalies v0.4711 KIAA0556 Zornitza Stark Gene: kiaa0556 has been classified as Green List (High Evidence).
Fetal anomalies v0.4710 KIAA0556 Zornitza Stark Tag new gene name tag was added to gene: KIAA0556.
Fetal anomalies v0.4710 BRF1 Zornitza Stark Marked gene: BRF1 as ready
Fetal anomalies v0.4710 BRF1 Zornitza Stark Gene: brf1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4710 BRF1 Zornitza Stark Classified gene: BRF1 as Green List (high evidence)
Fetal anomalies v0.4710 BRF1 Zornitza Stark Gene: brf1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4709 IFT74 Zornitza Stark Marked gene: IFT74 as ready
Fetal anomalies v0.4709 IFT74 Zornitza Stark Gene: ift74 has been classified as Green List (High Evidence).
Fetal anomalies v0.4709 IFT74 Zornitza Stark Phenotypes for gene: IFT74 were changed from ?Bardet-Biedl syndrome 22 - MIM#617119; Joubert syndrome 40 - MIM#619582 to Bardet-Biedl syndrome 22 - MIM#617119; Joubert syndrome 40 - MIM#619582
Fetal anomalies v0.4708 IFT74 Zornitza Stark Classified gene: IFT74 as Green List (high evidence)
Fetal anomalies v0.4708 IFT74 Zornitza Stark Gene: ift74 has been classified as Green List (High Evidence).
Fetal anomalies v0.4707 BRF1 Krithika Murali gene: BRF1 was added
gene: BRF1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: BRF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BRF1 were set to 25561519; 25561519; 27748960
Phenotypes for gene: BRF1 were set to Cerebellofaciodental syndrome - MIM#616202
Review for gene: BRF1 was set to GREEN
Added comment: Cerebellofaciodental syndrome is an autosomal recessive neurodevelopmental disorder characterized by delayed development, intellectual disability, abnormal facial and dental findings, and cerebellar hypoplasia.

At least 5 unrelated families and a zebrafish model.
Sources: Literature
Fetal anomalies v0.4707 FAM149B1 Zornitza Stark Marked gene: FAM149B1 as ready
Fetal anomalies v0.4707 FAM149B1 Zornitza Stark Gene: fam149b1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4707 FAM149B1 Zornitza Stark Classified gene: FAM149B1 as Green List (high evidence)
Fetal anomalies v0.4707 FAM149B1 Zornitza Stark Gene: fam149b1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4706 CCDC28B Zornitza Stark Marked gene: CCDC28B as ready
Fetal anomalies v0.4706 CCDC28B Zornitza Stark Gene: ccdc28b has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4706 CCDC28B Zornitza Stark Phenotypes for gene: CCDC28B were changed from Joubert syndrome to Joubert syndrome, MONDO:0018772
Fetal anomalies v0.4705 CCDC28B Zornitza Stark Classified gene: CCDC28B as Amber List (moderate evidence)
Fetal anomalies v0.4705 CCDC28B Zornitza Stark Gene: ccdc28b has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4704 ARL3 Zornitza Stark Marked gene: ARL3 as ready
Fetal anomalies v0.4704 ARL3 Zornitza Stark Gene: arl3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4704 ARL3 Zornitza Stark Classified gene: ARL3 as Green List (high evidence)
Fetal anomalies v0.4704 ARL3 Zornitza Stark Gene: arl3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4703 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Fetal anomalies v0.4702 MTX2 Krithika Murali gene: MTX2 was added
gene: MTX2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MTX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTX2 were set to 32917887
Phenotypes for gene: MTX2 were set to Mandibuloacral dysplasia progeroid syndrome - MIM#619127
Review for gene: MTX2 was set to GREEN
Added comment: Biallelic variants associated with severe progeroid form of MAD
Sources: Literature
Fetal anomalies v0.4702 TMEM218 Krithika Murali gene: TMEM218 was added
gene: TMEM218 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TMEM218 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM218 were set to 33791682; 25161209
Phenotypes for gene: TMEM218 were set to Joubert syndrome 39 - MIM#619562
Review for gene: TMEM218 was set to GREEN
Added comment: Associated with Jouberty syndrome. Occipital encephalocele reported in 5 fetuses.
Sources: Literature
Fetal anomalies v0.4702 NID1 Krithika Murali gene: NID1 was added
gene: NID1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: NID1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NID1 were set to 23674478; 25558065; 12480912; 30773799
Phenotypes for gene: NID1 were set to Dandy-Walker malformation and occipital cephalocele; Hydrocephalus with or without seizures
Review for gene: NID1 was set to GREEN
Added comment: No OMIM gene disease association. Monoallelic variants associated with brain anomalies including hydrocephalus, Dandy Walker malformation and occipital cephalocele.
-
Sources: Literature
Fetal anomalies v0.4702 KIAA0556 Krithika Murali gene: KIAA0556 was added
gene: KIAA0556 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: KIAA0556 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA0556 were set to 26714646; 27245168
Phenotypes for gene: KIAA0556 were set to Joubert syndrome 26 - MIM#616784
Review for gene: KIAA0556 was set to GREEN
Added comment: Associated with Joubert syndrome.

5 individuals from two families reported, supportive mouse model.

New HGNC approved name is KATNIP.
Sources: Literature
Fetal anomalies v0.4702 IFT74 Krithika Murali gene: IFT74 was added
gene: IFT74 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: IFT74 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFT74 were set to 33531668; 27486776; 32144365
Phenotypes for gene: IFT74 were set to ?Bardet-Biedl syndrome 22 - MIM#617119; Joubert syndrome 40 - MIM#619582
Review for gene: IFT74 was set to GREEN
Added comment: Biallelic variants associated with both Joubert and Bardet-Biedl syndrome phenotype - multiple congenital anomalies reported.
Sources: Literature
Fetal anomalies v0.4702 FAM149B1 Krithika Murali gene: FAM149B1 was added
gene: FAM149B1 was added to Fetal anomalies. 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 syndrome 36 - MIM#618763
Review for gene: FAM149B1 was set to GREEN
Added comment: Biallelic variants associated with Joubert syndrome in 4 unrelated families. Reported characteristics in published cases includes macrocephaly, mesoaxial polydactyly and cleft lip
Sources: Literature
Fetal anomalies v0.4702 CCDC28B Krithika Murali gene: CCDC28B was added
gene: CCDC28B was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CCDC28B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC28B were set to 32139166
Phenotypes for gene: CCDC28B were set to Joubert syndrome
Review for gene: CCDC28B was set to AMBER
Added comment: No new publications since last PanelApp review May 2020

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PMID: 32139166 - Single family with Joubert syndrome. Patient was homozygous for a missense, with polydactyly, severe ID, and the molar tooth sign observed in MRI. Sibling fetus MRI showed vermis hypoplasia, and was also homozygous for the variant. Parents confirmed unaffected carriers. Knockdown of CCDC28B in human TERT retinal pigment epithelial cells reduced both the number and length of cilia 430C-T variant is postulated to be a modifier of BBS.
Sources: Literature
Fetal anomalies v0.4702 ARL3 Krithika Murali gene: ARL3 was added
gene: ARL3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ARL3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARL3 were set to 30269812; 16565502
Phenotypes for gene: ARL3 were set to Joubert syndrome 35- MIM#618161
Review for gene: ARL3 was set to GREEN
Added comment: Associated with Joubert syndrome with antenatally detectable features including renal and brain anomalies
Sources: Literature
Fetal anomalies v0.4702 MORC2 Zornitza Stark Marked gene: MORC2 as ready
Fetal anomalies v0.4702 MORC2 Zornitza Stark Gene: morc2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4702 MORC2 Zornitza Stark Classified gene: MORC2 as Red List (low evidence)
Fetal anomalies v0.4702 MORC2 Zornitza Stark Gene: morc2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4701 MINPP1 Zornitza Stark Marked gene: MINPP1 as ready
Fetal anomalies v0.4701 MINPP1 Zornitza Stark Gene: minpp1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4701 MINPP1 Zornitza Stark Classified gene: MINPP1 as Green List (high evidence)
Fetal anomalies v0.4701 MINPP1 Zornitza Stark Gene: minpp1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4700 MORC2 Krithika Murali gene: MORC2 was added
gene: MORC2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MORC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MORC2 were set to 32693025
Phenotypes for gene: MORC2 were set to Developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy - MIM#619090
Review for gene: MORC2 was set to RED
Added comment: No new publications since last PanelApp review Dec 2020. No antenatal features reported.

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MORC2 variants have commonly been associated with CMT, presenting axonal neuropathy with progressive weakness, muscle cramps and sensory impairment. However, Sacoto et al (2020) (PMID: 32693025) present a cohort of 20 individuals (19 kindreds) with a neurodevelopmental disorder characterised by DD, ID (18/20 - mild to severe), short stature (18/20), microcephaly (15/20) and variable craniofacial dysmorphisms. Hearing loss was observed in 11/19 subjects, primarily SNHL.
Sources: Literature
Fetal anomalies v0.4700 NCAPD2 Zornitza Stark Marked gene: NCAPD2 as ready
Fetal anomalies v0.4700 NCAPD2 Zornitza Stark Gene: ncapd2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4700 NCAPD2 Zornitza Stark Classified gene: NCAPD2 as Green List (high evidence)
Fetal anomalies v0.4700 NCAPD2 Zornitza Stark Gene: ncapd2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4699 MINPP1 Krithika Murali gene: MINPP1 was added
gene: MINPP1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MINPP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MINPP1 were set to 33257696; 33168985
Phenotypes for gene: MINPP1 were set to Pontocerebellar hypoplasia, type 16 - MIM#619527
Review for gene: MINPP1 was set to GREEN
Added comment: Biallelic LoF variants associated with pontocerebellar hypoplasia. Early-onset progressive microcephaly is a phenotypic feature with one affected individual reported to have prenatal evidence of microcephaly associated with increased thalami echogenicity (PMID 33257696)
Sources: Literature
Fetal anomalies v0.4699 NCAPD2 Zornitza Stark gene: NCAPD2 was added
gene: NCAPD2 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: NCAPD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NCAPD2 were set to 31056748; 27737959; 28097321
Phenotypes for gene: NCAPD2 were set to Microcephaly 21, primary, autosomal recessive; OMIM #617983
Review for gene: NCAPD2 was set to GREEN
Added comment: Three families reported: 1 family with 2 sibs with microcephaly and ID, and homozygous NCAPD2 mutation, which segregated with disease. No functional evidence. 1 family with 1 affected and homozygous NCAPD2 mutation, which segregated with disease. Patient fibroblasts showed impaired chromosome segregation and abnormal recovery from mitotic condensation compared to controls. 1 family with 2 sibs with microcephaly, growth retardation, and ID, and homozygous NCAPD2 mutation, which segregated with disease. Functional studies of the variants and studies of patient cells were not performed.

IUGR reported.
Sources: Expert Review
Fetal anomalies v0.4698 NSRP1 Zornitza Stark Marked gene: NSRP1 as ready
Fetal anomalies v0.4698 NSRP1 Zornitza Stark Gene: nsrp1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4698 NSRP1 Zornitza Stark Classified gene: NSRP1 as Green List (high evidence)
Fetal anomalies v0.4698 NSRP1 Zornitza Stark Gene: nsrp1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4697 NSRP1 Zornitza Stark gene: NSRP1 was added
gene: NSRP1 was added to Fetal anomalies. Sources: Expert Review
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 Neurodevelopmental disorder, MONDO:0700092, NSRP1-related; 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.

Structural brain abnormalities.
Sources: Expert Review
Mendeliome v0.11113 NSRP1 Zornitza Stark edited their review of gene: NSRP1: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, NSRP1-related, Epilepsy, Cerebral palsy, microcephaly, Intellectual disability
Fetal anomalies v0.4696 NUF2 Zornitza Stark Marked gene: NUF2 as ready
Fetal anomalies v0.4696 NUF2 Zornitza Stark Gene: nuf2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4696 NUF2 Zornitza Stark gene: NUF2 was added
gene: NUF2 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: NUF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NUF2 were set to 33721060
Phenotypes for gene: NUF2 were set to Syndromic disease, MONDO:0002254; microcephaly; short stature; bilateral vocal cord paralysis; micrognathia; atrial septal defect
Review for gene: NUF2 was set to RED
Added comment: PMID: 33721060 - de novo missense variant identified in one male patient with microcephaly and short stature, with additional features, such as bilateral vocal cord paralysis, micrognathia and atrial septal defect.
Sources: Expert Review
Fetal anomalies v0.4695 NUP188 Zornitza Stark Marked gene: NUP188 as ready
Fetal anomalies v0.4695 NUP188 Zornitza Stark Gene: nup188 has been classified as Green List (High Evidence).
Fetal anomalies v0.4695 NUP188 Zornitza Stark Classified gene: NUP188 as Green List (high evidence)
Fetal anomalies v0.4695 NUP188 Zornitza Stark Gene: nup188 has been classified as Green List (High Evidence).
Fetal anomalies v0.4694 NUP188 Zornitza Stark gene: NUP188 was added
gene: NUP188 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: NUP188 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP188 were set to 32021605; 28726809; 32275884
Phenotypes for gene: NUP188 were set to Sandestig-Stefanova syndrome, 618804; microcephaly; ID; cataract; structural brain abnormalities
Review for gene: NUP188 was set to GREEN
Added comment: 8 unrelated individuals reported.
Sources: Expert Review
Fetal anomalies v0.4693 NUP85 Zornitza Stark Marked gene: NUP85 as ready
Fetal anomalies v0.4693 NUP85 Zornitza Stark Gene: nup85 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4693 NUP85 Zornitza Stark Classified gene: NUP85 as Amber List (moderate evidence)
Fetal anomalies v0.4693 NUP85 Zornitza Stark Gene: nup85 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4692 NUP85 Zornitza Stark gene: NUP85 was added
gene: NUP85 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: NUP85 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP85 were set to 34170319
Phenotypes for gene: NUP85 were set to Microcephaly, MONDO:0001149, NUP85-related
Review for gene: NUP85 was set to AMBER
Added comment: PMID: 34170319 - Ravindran et al 2021 report two pedigrees with an MCPH-SCKS phenotype spectrum without SRNS. In the first family, a 9 yo female, with consanguineous parents, is reported to have a missense variant in NUP85 (c.932G > A; p.R311Q). Intrauterine growth restriction was noticed. At birth microcephaly was observed (OFC < 3rd centile, < −3.6 SD) as well as hypotrophy [weight −2.8 SD), length 45 cm (−2.7 SD), both <3rd centile], facial dysmorphism, syndactyly, long and thin fingers, and bilateral pes adductus. She has severe developmental delay with strongly delayed motor milestones and absent speech. Drug-resistant, genetic epilepsy with focal-onset seizures started in the first year of life. She had no clinical, laboratory or radiological findings indicative of kidney dysfunction. In the second family, compound heterozygous missense variants in NUP85 were detected (c.1109A > G, c.1589 T > C;p.N370S, p.M530T ) in a fetus. MRI of the fetal brain at 24 + 2 GW indicated complete agenesis of the corpus callosum, abnormal sulcation in the left frontal lobe, nodularity of the frontal horn and trigone with focal puckering of the left lateral ventricle.

Variants in this gene are also associated with nephrotic syndrome.
Sources: Expert Review
Fetal anomalies v0.4691 PUS7 Zornitza Stark Marked gene: PUS7 as ready
Fetal anomalies v0.4691 PUS7 Zornitza Stark Gene: pus7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4691 PUS7 Zornitza Stark Classified gene: PUS7 as Amber List (moderate evidence)
Fetal anomalies v0.4691 PUS7 Zornitza Stark Gene: pus7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4690 PUS7 Zornitza Stark reviewed gene: PUS7: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature, OMIM #618342; Mode of inheritance: None
Fetal anomalies v0.4690 PTPN23 Zornitza Stark Marked gene: PTPN23 as ready
Fetal anomalies v0.4690 PTPN23 Zornitza Stark Gene: ptpn23 has been classified as Green List (High Evidence).
Fetal anomalies v0.4690 PTPN23 Zornitza Stark Classified gene: PTPN23 as Green List (high evidence)
Fetal anomalies v0.4690 PTPN23 Zornitza Stark Gene: ptpn23 has been classified as Green List (High Evidence).
Fetal anomalies v0.4689 PUS7 Belinda Chong gene: PUS7 was added
gene: PUS7 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PUS7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PUS7 were set to 30526862; 30778726; 31583274
Phenotypes for gene: PUS7 were set to Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature; OMIM #618342
Review for gene: PUS7 was set to RED
gene: PUS7 was marked as current diagnostic
Added comment: Onset at infancy

11 patients from 6 families with ID, speech delay, short stature, microcephaly, and aggressive behavior, with homozygous PUS7 mutations, which segregated with disease.
Sources: Literature
Fetal anomalies v0.4689 PRIM1 Zornitza Stark Marked gene: PRIM1 as ready
Fetal anomalies v0.4689 PRIM1 Zornitza Stark Gene: prim1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4689 PRIM1 Zornitza Stark Classified gene: PRIM1 as Amber List (moderate evidence)
Fetal anomalies v0.4689 PRIM1 Zornitza Stark Gene: prim1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4688 PPP1R15B Zornitza Stark Marked gene: PPP1R15B as ready
Fetal anomalies v0.4688 PPP1R15B Zornitza Stark Gene: ppp1r15b has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4688 PPP1R15B Zornitza Stark Classified gene: PPP1R15B as Amber List (moderate evidence)
Fetal anomalies v0.4688 PPP1R15B Zornitza Stark Gene: ppp1r15b has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4687 PPIL1 Zornitza Stark Marked gene: PPIL1 as ready
Fetal anomalies v0.4687 PPIL1 Zornitza Stark Gene: ppil1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4687 PPIL1 Zornitza Stark Classified gene: PPIL1 as Green List (high evidence)
Fetal anomalies v0.4687 PPIL1 Zornitza Stark Gene: ppil1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4686 PTPN23 Belinda Chong gene: PTPN23 was added
gene: PTPN23 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PTPN23 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTPN23 were set to 31395947; 29899372; 29090338; 27848944; 25558065
Phenotypes for gene: PTPN23 were set to Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity, MIM# 618890
Review for gene: PTPN23 was set to GREEN
gene: PTPN23 was marked as current diagnostic
Added comment: Onset at birth or early infancy.

Over 10 families reported with an autosomal recessive neurologic disorder characterised by global developmental delay apparent from early infancy, poor overall growth often with microcephaly (6/10), impaired intellectual development with delayed or absent speech, axial hypotonia, and peripheral spasticity. Additional common but variable features include early-onset seizures, optic atrophy with poor visual fixation, and dysmorphic facial features. Brain imaging shows cerebral atrophy, poor or absent myelination with loss of white matter volume, and often hypoplasia of the corpus callosum and/or cerebellum.
Sources: Literature
Fetal anomalies v0.4686 PRIM1 Belinda Chong gene: PRIM1 was added
gene: PRIM1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PRIM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRIM1 were set to 33060134
Phenotypes for gene: PRIM1 were set to Microcephalic primordial dwarfism, MONDO:0017950
Review for gene: PRIM1 was set to AMBER
gene: PRIM1 was marked as current diagnostic
Added comment: - PMID: 33060134 (2020) - From a cohort of 220 families with microcephalic dwarfism spectrum disorders (OFC ≤−4 SD; height ≤−2 SD), three families (4 individuals) were identified with the same homozygous intronic variant (c.638+36C>G) in PRIM1. This variant was present in gnomAD in 2 individuals across all populations, but only in a heterozygous state. Haplotype analysis indicated that all three families share a distant common ancestor - i.e. confirmed founder variant.
Authors subsequently identified a single individual with compound heterozygous PRIM1 variants (c.103+1G>T, c.901T>C) from the DDD study, who also presented microcephaly and short stature (OFC ≤−3 SD; height ≤−3 SD).

Clinical overlap was evident in all 5 individuals, presenting extreme pre- and postnatal growth restriction, severe microcephaly (OFC −6.0 ± 1.5 SD) with simplified gyri appearance, hypothyroidism, hypo/agammaglobulinaemia, and lymphopaenia accompanied by intermittent anaemia/thrombocytopaenia. All had chronic respiratory symptoms, and four died in early childhood from respiratory or GI infections.

Functional studies demonstrated reduced PRIM1 protein levels, replication fork defects and prolonged S-phase duration in PRIM1-deficient cells. The resulting delay to the cell cycle and inability to sustain sufficient cell proliferation provides a likely mechanism for the presenting phenotype.
Sources: Literature
Fetal anomalies v0.4686 PPP1R15B Belinda Chong gene: PPP1R15B was added
gene: PPP1R15B was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PPP1R15B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPP1R15B were set to 26159176; 26307080; 27640355
Phenotypes for gene: PPP1R15B were set to Microcephaly, short stature, and impaired glucose metabolism 2, MIM# 616817
Review for gene: PPP1R15B was set to AMBER
gene: PPP1R15B was marked as current diagnostic
Added comment: Three unrelated families reported, two with the same variant. Phenotype in family reported in PMID 27640355 included infantile cirrhosis requiring transplantation.
Sources: Literature
Photosensitivity Syndromes v1.0 RECQL Dean Phelan gene: RECQL was added
gene: RECQL was added to Photosensitivity Syndromes. Sources: Literature
Mode of inheritance for gene: RECQL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RECQL were set to PMID: 35025765
Phenotypes for gene: RECQL were set to Photosensitivity; facial dysmorphism; xeropthalmia; skeletal abnormalities
Review for gene: RECQL was set to AMBER
Added comment: PMID: 35025765
- Homozygous missense variants identified in two seemingly unrelated families with genome instability disorder. Both families had the same missense variant. Phenotype was progeriod facial features, skin photosensitivity, xeroderma, and slender elongated thumbs.
Sources: Literature
Heterotaxy v1.15 AL117258.1 Zornitza Stark Marked gene: AL117258.1 as ready
Heterotaxy v1.15 AL117258.1 Zornitza Stark Gene: al117258.1 has been classified as Green List (High Evidence).
Microcephaly v1.111 CPSF3 Alison Yeung Phenotypes for gene: CPSF3 were changed from Neurodevelopmental disorder, CPSF3-related, MONDO:0700092 to Neurodevelopmental disorder, CPSF3-related, MONDO:0700092
Microcephaly v1.110 CPSF3 Alison Yeung Classified gene: CPSF3 as Green List (high evidence)
Microcephaly v1.110 CPSF3 Alison Yeung Gene: cpsf3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4686 PPIL1 Belinda Chong gene: PPIL1 was added
gene: PPIL1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PPIL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPIL1 were set to 33220177
Phenotypes for gene: PPIL1 were set to Pontocerebellar hypoplasia, type 14, MIM# 619301; microcephaly; seizures
Review for gene: PPIL1 was set to GREEN
gene: PPIL1 was marked as current diagnostic
Added comment: The patients presented at birth with severe microcephaly (-2 to -6 SD), which progressed postnatally (-4 to -8 SD)

17 individuals from 9 unrelated families reported with bi-allelic variants in the gene and PCH, microcephaly, hypotonia, seizures, severe DD/ID. Mouse models support gene-disease association.
Sources: Literature
Microcephaly v1.110 CPSF3 Alison Yeung Phenotypes for gene: CPSF3 were changed from Intellectual disability syndrome to Neurodevelopmental disorder, CPSF3-related, MONDO:0700092
Heterotaxy v1.15 AL117258.1 Zornitza Stark Phenotypes for gene: AL117258.1 were changed from Heterotaxy, MONDO:0018677; congenital heart defects to Heterotaxy, MONDO:0018677; congenital heart defects
Microcephaly v1.110 CPSF3 Alison Yeung Classified gene: CPSF3 as Green List (high evidence)
Microcephaly v1.110 CPSF3 Alison Yeung Gene: cpsf3 has been classified as Green List (High Evidence).
Microcephaly v1.109 CPSF3 Alison Yeung Marked gene: CPSF3 as ready
Heterotaxy v1.15 AL117258.1 Zornitza Stark Phenotypes for gene: AL117258.1 were changed from Heterotaxy; congenital heart defects to Heterotaxy, MONDO:0018677; congenital heart defects
Microcephaly v1.109 CPSF3 Alison Yeung Gene: cpsf3 has been removed from the panel.
Genetic Epilepsy v0.1460 CPSF3 Alison Yeung Classified gene: CPSF3 as Green List (high evidence)
Genetic Epilepsy v0.1460 CPSF3 Alison Yeung Gene: cpsf3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1461 CPSF3 Alison Yeung Phenotypes for gene: CPSF3 were changed from Neurodevelopmental disorder, CPSF3-related, MONDO:0700092 to Neurodevelopmental disorder, CPSF3-related, MONDO:0700092
Heterotaxy v1.14 AL117258.1 Zornitza Stark Classified gene: AL117258.1 as Green List (high evidence)
Heterotaxy v1.14 AL117258.1 Zornitza Stark Gene: al117258.1 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.195 AL117258.1 Zornitza Stark Phenotypes for gene: AL117258.1 were changed from Heterotaxy, MONDO:0018677; congenital heart defects to Heterotaxy, MONDO:0018677; congenital heart defects
Genetic Epilepsy v0.1461 CPSF3 Alison Yeung Phenotypes for gene: CPSF3 were changed from Neurodevelopmental disorder, CPSF3-related, MONDO:0700092 to Neurodevelopmental disorder, CPSF3-related, MONDO:0700092
Congenital Heart Defect v0.194 AL117258.1 Zornitza Stark Marked gene: AL117258.1 as ready
Congenital Heart Defect v0.194 AL117258.1 Zornitza Stark Gene: al117258.1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1460 CPSF3 Alison Yeung Phenotypes for gene: CPSF3 were changed from Intellectual disability syndrome to Neurodevelopmental disorder, CPSF3-related, MONDO:0700092
Congenital Heart Defect v0.194 AL117258.1 Zornitza Stark Phenotypes for gene: AL117258.1 were changed from Heterotaxy; congenital heart defects to Heterotaxy, MONDO:0018677; congenital heart defects
Cardiomyopathy_Paediatric v0.126 CRLS1 Zornitza Stark Marked gene: CRLS1 as ready
Cardiomyopathy_Paediatric v0.126 CRLS1 Zornitza Stark Gene: crls1 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.109 HIST1H4E Paul De Fazio gene: HIST1H4E was added
gene: HIST1H4E was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: HIST1H4E was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: HIST1H4E were set to 35202563
Phenotypes for gene: HIST1H4E were set to Neurodevelopmental disorder, HIST1H4E-related MONDO:0700092
Review for gene: HIST1H4E was set to GREEN
gene: HIST1H4E was marked as current diagnostic
Added comment: HGNC recognised gene name: H4C5
17 patients identified with de novo missense variants affecting Lys31, Pro32, Arg35, Leu37, Arg40 (recurrent), Arg45 (recurrent), Tyr98 (recurrent). All individuals had ID/dev delay. Additional phenotypes in some but not all individuals included epilepsy, hypotonia, facial dysmorphism. Most had reduced birth length, OFC, weight (-1 to -3SD). OFC at most recent exam (age range 11 months to 18 years) ranged from -0.15SD to < -4SD. 10/17 had OFC < -3SD.
A zebrafish model has developmental defects.
Sources: Literature
Cardiomyopathy_Paediatric v0.126 CRLS1 Zornitza Stark Phenotypes for gene: CRLS1 were changed from 35147173 to Mitochondrial disease MONDO:0044970 CRLS1-related
Cardiomyopathy_Paediatric v0.125 CRLS1 Zornitza Stark Publications for gene: CRLS1 were set to
Cardiomyopathy_Paediatric v0.124 CRLS1 Zornitza Stark Classified gene: CRLS1 as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v0.124 CRLS1 Zornitza Stark Gene: crls1 has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v1.121 CRLS1 Zornitza Stark Classified gene: CRLS1 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.121 CRLS1 Zornitza Stark Gene: crls1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.121 CRLS1 Zornitza Stark Marked gene: CRLS1 as ready
Deafness_IsolatedAndComplex v1.121 CRLS1 Zornitza Stark Gene: crls1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1460 CPSF3 Alison Yeung Classified gene: CPSF3 as Green List (high evidence)
Genetic Epilepsy v0.1460 CPSF3 Alison Yeung Gene: cpsf3 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.123 CRLS1 Michelle Torres reviewed gene: CRLS1: Rating: AMBER; Mode of pathogenicity: None; Publications: 35147173; Phenotypes: Mitochondrial disease MONDO:0044970 CRLS1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.121 CRLS1 Zornitza Stark Classified gene: CRLS1 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.121 CRLS1 Zornitza Stark Gene: crls1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1459 CPSF3 Alison Yeung Marked gene: CPSF3 as ready
Genetic Epilepsy v0.1459 CPSF3 Alison Yeung Gene: cpsf3 has been removed from the panel.
Congenital Heart Defect v0.193 AL117258.1 Zornitza Stark Classified gene: AL117258.1 as Green List (high evidence)
Congenital Heart Defect v0.193 AL117258.1 Zornitza Stark Gene: al117258.1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.123 CRLS1 Michelle Torres Deleted their review
Intellectual disability syndromic and non-syndromic v0.4529 CRLS1 Zornitza Stark Marked gene: CRLS1 as ready
Intellectual disability syndromic and non-syndromic v0.4529 CRLS1 Zornitza Stark Gene: crls1 has been classified as Green List (High Evidence).
Mendeliome v0.11113 RECQL Alison Yeung Marked gene: RECQL as ready
Mendeliome v0.11113 RECQL Alison Yeung Gene: recql has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11113 RECQL Alison Yeung Classified gene: RECQL as Amber List (moderate evidence)
Mendeliome v0.11113 RECQL Alison Yeung Gene: recql has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4529 CRLS1 Zornitza Stark Classified gene: CRLS1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4529 CRLS1 Zornitza Stark Gene: crls1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.120 CRLS1 Michelle Torres gene: CRLS1 was added
gene: CRLS1 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: CRLS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRLS1 were set to 35147173
Phenotypes for gene: CRLS1 were set to Mitochondrial disease MONDO:0044970 CRLS1-related
Review for gene: CRLS1 was set to GREEN
Added comment: - Three families (4 individuals) with cardiolipin deficiency.
- Two families (one consanguineous with 2 affected siblings) with homozygous the p.(Ile109Asn) had infantile progressive encephalopathy, bull’s eye maculopathy, auditory neuropathy, diabetes insipidus, autonomic instability, cardiac defects and early death.
- The fourth individual cHet p.(Ala172Asp) and p.(Leu217Phe) presented with chronic encephalopathy with neurodevelopmental regression, congenital nystagmus with decreased vision, sensorineural hearing loss, failure to thrive and acquired microcephaly.
- Functional studies on patient cells showed increased levels of the substrate of CRLS1 and impaired mitochondrial morphology and biogenesis

*2 individuals with auditory neuropathy and one with sensorineural hearing loss
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4528 ZBTB7A Zornitza Stark Classified gene: ZBTB7A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4528 ZBTB7A Zornitza Stark Gene: zbtb7a has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.101 ZBTB7A Zornitza Stark Classified gene: ZBTB7A as Green List (high evidence)
Macrocephaly_Megalencephaly v0.101 ZBTB7A Zornitza Stark Gene: zbtb7a has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.101 ZBTB7A Zornitza Stark Marked gene: ZBTB7A as ready
Macrocephaly_Megalencephaly v0.101 ZBTB7A Zornitza Stark Gene: zbtb7a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4528 CRLS1 Zornitza Stark reviewed gene: CRLS1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Microcephaly v1.109 HIST1H4C Paul De Fazio reviewed gene: HIST1H4C: Rating: GREEN; Mode of pathogenicity: None; Publications: 35202563; Phenotypes: Tessadori-van Haaften neurodevelopmental syndrome 1 MIM#619758, Neurodevelopmental disorder, HIST1H4C-related MONDO:0700092; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.4528 HIST1H4E Alison Yeung Classified gene: HIST1H4E as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4528 HIST1H4E Alison Yeung Gene: hist1h4e has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.101 ZBTB7A Zornitza Stark Classified gene: ZBTB7A as Green List (high evidence)
Macrocephaly_Megalencephaly v0.101 ZBTB7A Zornitza Stark Gene: zbtb7a has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.123 CRLS1 Michelle Torres gene: CRLS1 was added
gene: CRLS1 was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: CRLS1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CRLS1 were set to 35147173
Review for gene: CRLS1 was set to AMBER
Added comment: - Three families (4 individuals) with cardiolipin deficiency.
- Two families (one consanguineous with 2 affected siblings) with homozygous the p.(Ile109Asn) had infantile progressive encephalopathy, bull’s eye maculopathy, auditory neuropathy, diabetes insipidus, autonomic instability, cardiac defects and early death.
- The fourth individual cHet p.(Ala172Asp) and p.(Leu217Phe) presented with chronic encephalopathy with neurodevelopmental regression, congenital nystagmus with decreased vision, sensorineural hearing loss, failure to thrive and acquired microcephaly.
- Functional studies on patient cells showed increased levels of the substrate of CRLS1 and impaired mitochondrial morphology and biogenesis

*Two individuals presented cardiac defects: one with LVNC, biventricular systolic dysfunction and evolved to HCM; the other one had biventricular dysfunction
Sources: Literature
Fetal anomalies v0.4686 HIST1H4C Paul De Fazio reviewed gene: HIST1H4C: Rating: GREEN; Mode of pathogenicity: None; Publications: 35202563; Phenotypes: Tessadori-van Haaften neurodevelopmental syndrome 1 MIM#619758, Neurodevelopmental disorder, HIST1H4C-related MONDO:0700092; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.4528 ZBTB7A Zornitza Stark Marked gene: ZBTB7A as ready
Intellectual disability syndromic and non-syndromic v0.4528 ZBTB7A Zornitza Stark Gene: zbtb7a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4528 ZBTB7A Zornitza Stark Classified gene: ZBTB7A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4528 ZBTB7A Zornitza Stark Gene: zbtb7a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4528 HIST1H4E Alison Yeung Classified gene: HIST1H4E as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4528 HIST1H4E Alison Yeung Gene: hist1h4e has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4527 HIST1H4E Alison Yeung Classified gene: HIST1H4E as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4527 HIST1H4E Alison Yeung Gene: hist1h4e has been classified as Green List (High Evidence).
Mitochondrial disease v0.702 CRLS1 Zornitza Stark Marked gene: CRLS1 as ready
Mitochondrial disease v0.702 CRLS1 Zornitza Stark Gene: crls1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4527 HIST1H4E Alison Yeung Classified gene: HIST1H4E as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4527 HIST1H4E Alison Yeung Gene: hist1h4e has been classified as Green List (High Evidence).
Mitochondrial disease v0.702 CRLS1 Zornitza Stark Classified gene: CRLS1 as Green List (high evidence)
Mitochondrial disease v0.702 CRLS1 Zornitza Stark Gene: crls1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4526 HIST1H4E Alison Yeung Marked gene: HIST1H4E as ready
Intellectual disability syndromic and non-syndromic v0.4526 HIST1H4E Alison Yeung Gene: hist1h4e has been removed from the panel.
Genetic Epilepsy v0.1459 CPSF3 Belinda Chong gene: CPSF3 was added
gene: CPSF3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CPSF3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPSF3 were set to 35121750
Phenotypes for gene: CPSF3 were set to Intellectual disability syndrome
Review for gene: CPSF3 was set to GREEN
gene: CPSF3 was marked as current diagnostic
Added comment: Study of a deficit of observed homozygous carriers of missense variants, versus an expected number in a set of 153,054 chip-genotyped Icelanders, to identify potentially pathogenic genotypes

Six homozygous carriers of missense variants in CPSF3 show severe intellectual disability, seizures, microcephaly, and abnormal muscle tone.

- Four identified through Icelandic geneology (p.Gly468Glu), three carrier couples total of four children who had died prematurely. Tested archival samples for two of these children, and confirm a homozygous genotype.
- Two of Mexican descent (p.Ile354Thr), first-degree cousins
Sources: Literature
Mendeliome v0.11112 HIST1H4E Alison Yeung Marked gene: HIST1H4E as ready
Mendeliome v0.11112 HIST1H4E Alison Yeung Gene: hist1h4e has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4526 HIST1H4D Zornitza Stark Marked gene: HIST1H4D as ready
Intellectual disability syndromic and non-syndromic v0.4526 HIST1H4D Zornitza Stark Gene: hist1h4d has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4526 HIST1H4D Zornitza Stark Classified gene: HIST1H4D as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.4526 HIST1H4D Zornitza Stark Gene: hist1h4d has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11112 HIST1H4E Alison Yeung Classified gene: HIST1H4E as Green List (high evidence)
Mendeliome v0.11112 HIST1H4E Alison Yeung Gene: hist1h4e has been classified as Green List (High Evidence).
Mendeliome v0.11111 HIST1H4D Zornitza Stark Marked gene: HIST1H4D as ready
Mendeliome v0.11111 HIST1H4D Zornitza Stark Gene: hist1h4d has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11111 HIST1H4D Zornitza Stark Classified gene: HIST1H4D as Amber List (moderate evidence)
Mendeliome v0.11111 HIST1H4D Zornitza Stark Gene: hist1h4d has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4525 ZBTB11 Zornitza Stark Classified gene: ZBTB11 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4525 ZBTB11 Zornitza Stark Gene: zbtb11 has been classified as Green List (High Evidence).
Mendeliome v0.11110 RECQL Dean Phelan gene: RECQL was added
gene: RECQL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RECQL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RECQL were set to PMID: 35025765
Phenotypes for gene: RECQL were set to Photosensitivity; facial dysmorphism; xeropthalmia; skeletal abnormalities
Review for gene: RECQL was set to AMBER
Added comment: PMID: 35025765
- Homozygous missense variants identified in two seemingly unrelated families with a genome instability disorder. Both families had the same missense variant. Phenotype was progeroid facial features, skin photosensitivity, xeroderma, and slender elongated thumbs.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4525 CPSF3 Alison Yeung Phenotypes for gene: CPSF3 were changed from Neurodevelopmental disorder, CPSF3-related, MONDO:0700092 to Neurodevelopmental disorder, CPSF3-related, MONDO:0700092
Mendeliome v0.11110 ZBTB11 Zornitza Stark Classified gene: ZBTB11 as Green List (high evidence)
Mendeliome v0.11110 ZBTB11 Zornitza Stark Gene: zbtb11 has been classified as Green List (High Evidence).
Microcephaly v1.109 CPSF3 Belinda Chong gene: CPSF3 was added
gene: CPSF3 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CPSF3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPSF3 were set to 35121750
Phenotypes for gene: CPSF3 were set to Intellectual disability syndrome
Review for gene: CPSF3 was set to GREEN
gene: CPSF3 was marked as current diagnostic
Added comment: Study of a deficit of observed homozygous carriers of missense variants, versus an expected number in a set of 153,054 chip-genotyped Icelanders, to identify potentially pathogenic genotypes

Six homozygous carriers of missense variants in CPSF3 show severe intellectual disability, seizures, microcephaly, and abnormal muscle tone.

- Four identified through Icelandic geneology (p.Gly468Glu), three carrier couples total of four children who had died prematurely. Tested archival samples for two of these children, and confirm a homozygous genotype.
- Two of Mexican descent (p.Ile354Thr), first-degree cousins
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4524 ZBTB11 Zornitza Stark Classified gene: ZBTB11 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4524 ZBTB11 Zornitza Stark Gene: zbtb11 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4524 CPSF3 Alison Yeung Marked gene: CPSF3 as ready
Intellectual disability syndromic and non-syndromic v0.4524 CPSF3 Alison Yeung Gene: cpsf3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4524 HIST1H4D Paul De Fazio changed review comment from: Single individual described with a de novo missense variant Arg41His (Arg40 in H4 nomenclature). Apart from langauge delay and moderate ID, phenotypes included facial dysmorphisms and cochlear abnormalities and arhinencephaly on MRI. Hearing was normal. Birth length, OFC, weight were all reduced (-2 to -2.5SD).
A zebrafish model has developmental defects.
Sources: Literature; to: HGNC recognised gene name: H4C4
Single individual described with a de novo missense variant Arg41His (Arg40 in H4 nomenclature). Apart from langauge delay and moderate ID, phenotypes included facial dysmorphisms and cochlear abnormalities and arhinencephaly on MRI. Hearing was normal. Birth length, OFC, weight were all reduced (-2 to -2.5SD).
A zebrafish model has developmental defects.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4524 CPSF3 Alison Yeung Phenotypes for gene: CPSF3 were changed from Intellectual disability syndrome to Neurodevelopmental disorder, CPSF3-related, MONDO:0700092
Congenital Heart Defect v0.192 AL117258.1 Melanie Marty gene: AL117258.1 was added
gene: AL117258.1 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: AL117258.1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AL117258.1 were set to 34903892
Phenotypes for gene: AL117258.1 were set to Heterotaxy; congenital heart defects
Review for gene: AL117258.1 was set to GREEN
Added comment: Gene also known as CIROP and LMLN2

Homozygous or compound heterozygous CIROP variants identified in 12 families with congenital heart defects associated with heterotaxy.

Functional tests performed on Xenopus and zebrafish embryos showed that CIROP was essential for left side symmetry and is expressed in ciliated left–right organisers.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4523 CPSF3 Alison Yeung Classified gene: CPSF3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4523 CPSF3 Alison Yeung Gene: cpsf3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4522 HIST1H4C Zornitza Stark Publications for gene: HIST1H4C were set to 28920961
Intellectual disability syndromic and non-syndromic v0.4521 HIST1H4C Zornitza Stark Phenotypes for gene: HIST1H4C were changed from Growth delay, microcephaly and intellectual disability to Tessadori-van Haaften neurodevelopmental syndrome 1 MIM#619758
Intellectual disability syndromic and non-syndromic v0.4520 NRCAM Alison Yeung Marked gene: NRCAM as ready
Intellectual disability syndromic and non-syndromic v0.4520 NRCAM Alison Yeung Gene: nrcam has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4520 CPSF3 Belinda Chong gene: CPSF3 was added
gene: CPSF3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CPSF3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPSF3 were set to 35121750
Phenotypes for gene: CPSF3 were set to Intellectual disability syndrome
Review for gene: CPSF3 was set to GREEN
gene: CPSF3 was marked as current diagnostic
Added comment: Study of a deficit of observed homozygous carriers of missense variants, versus an expected number in a set of 153,054 chip-genotyped Icelanders, to identify potentially pathogenic genotypes

Six homozygous carriers of missense variants in CPSF3 show severe intellectual disability, seizures, microcephaly, and abnormal muscle tone.

- Four identified through Icelandic geneology (p.Gly468Glu), three carrier couples total of four children who had died prematurely. Tested archival samples for two of these children, and confirm a homozygous genotype.
- Two of Mexican descent (p.Ile354Thr), first-degree cousins
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4520 NRCAM Alison Yeung Classified gene: NRCAM as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4520 NRCAM Alison Yeung Gene: nrcam has been classified as Green List (High Evidence).
Mendeliome v0.11109 HIST1H4E Paul De Fazio changed review comment from: 17 patients identified with de novo missense variants affecting Lys31, Pro32, Arg35, Leu37, Arg40 (recurrent), Arg45 (recurrent), Tyr98 (recurrent). All individuals had ID/dev delay. Additional phenotypes in some but not all individuals included epilepsy, hypotonia, facial dysmorphism. Most had reduced birth length, OFC, weight (-1 to -3SD).
A zebrafish model has developmental defects.
Sources: Literature; to: HGNC recognised gene: H4C5
17 patients identified with de novo missense variants affecting Lys31, Pro32, Arg35, Leu37, Arg40 (recurrent), Arg45 (recurrent), Tyr98 (recurrent). All individuals had ID/dev delay. Additional phenotypes in some but not all individuals included epilepsy, hypotonia, facial dysmorphism. Most had reduced birth length, OFC, weight (-1 to -3SD).
A zebrafish model has developmental defects.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4520 NRCAM Alison Yeung Classified gene: NRCAM as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4520 NRCAM Alison Yeung Gene: nrcam has been classified as Green List (High Evidence).
Heterotaxy v1.13 AL117258.1 Melanie Marty gene: AL117258.1 was added
gene: AL117258.1 was added to Heterotaxy. Sources: Literature
Mode of inheritance for gene: AL117258.1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AL117258.1 were set to 34903892
Phenotypes for gene: AL117258.1 were set to Heterotaxy; congenital heart defects
Review for gene: AL117258.1 was set to GREEN
Added comment: Gene also known as CIROP and LMLN2

Homozygous or compound heterozygous CIROP variants identified in 12 families with congenital heart defects associated with heterotaxy.

Functional tests performed on Xenopus and zebrafish embryos showed that CIROP was essential for left side symmetry and is expressed in ciliated left–right organisers.
Sources: Literature
Mendeliome v0.11109 HIST1H4C Zornitza Stark Phenotypes for gene: HIST1H4C were changed from Growth delay, microcephaly and intellectual disability to Tessadori-van Haaften neurodevelopmental syndrome 1 MIM#619758
Intellectual disability syndromic and non-syndromic v0.4519 HIST1H4E Paul De Fazio changed review comment from: 17 patients identified with de novo missense variants affecting Lys31, Pro32, Arg35, Leu37, Arg40 (recurrent), Arg45 (recurrent), Tyr98 (recurrent). All individuals had ID/dev delay. Additional phenotypes in some but not all individuals included epilepsy, hypotonia, facial dysmorphism. Most had reduced birth length, OFC, weight (-1 to -3SD).
A zebrafish model has developmental defects.
Sources: Literature; to: HGNC recognised gene: H4C5
17 patients identified with de novo missense variants affecting Lys31, Pro32, Arg35, Leu37, Arg40 (recurrent), Arg45 (recurrent), Tyr98 (recurrent). All individuals had ID/dev delay. Additional phenotypes in some but not all individuals included epilepsy, hypotonia, facial dysmorphism. Most had reduced birth length, OFC, weight (-1 to -3SD).
A zebrafish model has developmental defects.
Sources: Literature
Mendeliome v0.11108 HIST1H4C Zornitza Stark Publications for gene: HIST1H4C were set to 28920961
Mendeliome v0.11107 HIST1H4C Paul De Fazio changed review comment from: 6 additional individuals with ID and dev delay. All variants were de novo. Lys92 (Lys91 in H4 nomenclature) and Pro33 (Pro32) were the only variants identified. Additional phenotypes in some but not all patients included hypotonia, facial dysmorphisms, conductive hearing loss. Most had reduced birth length, OFC, weight (-1 to -2.5SD).
A zebrafish model has developmental defects.; to: HGNC recognised gene: H4C3
6 additional individuals with ID and dev delay. All variants were de novo. Lys92 (Lys91 in H4 nomenclature) and Pro33 (Pro32) were the only variants identified. Additional phenotypes in some but not all patients included hypotonia, facial dysmorphisms, conductive hearing loss. Most had reduced birth length, OFC, weight (-1 to -2.5SD).
A zebrafish model has developmental defects.
Intellectual disability syndromic and non-syndromic v0.4519 HIST1H4C Paul De Fazio changed review comment from: 6 additional individuals with ID and dev delay. All variants were de novo. Lys92 (Lys91 in H4 nomenclature) and Pro33 (Pro32) were the only variants identified. Additional phenotypes in some but not all patients included hypotonia, facial dysmorphisms, conductive hearing loss. Most had reduced birth length, OFC, weight (-1 to -2.5SD).
A zebrafish model has developmental defects.; to: HGNC recognised gene name: H4C3
6 additional individuals with ID and dev delay. All variants were de novo. Lys92 (Lys91 in H4 nomenclature) and Pro33 (Pro32) were the only variants identified. Additional phenotypes in some but not all patients included hypotonia, facial dysmorphisms, conductive hearing loss. Most had reduced birth length, OFC, weight (-1 to -2.5SD).
A zebrafish model has developmental defects.
Mendeliome v0.11107 CPSF3 Alison Yeung Marked gene: CPSF3 as ready
Mendeliome v0.11107 CPSF3 Alison Yeung Gene: cpsf3 has been classified as Green List (High Evidence).
Mendeliome v0.11107 AL117258.1 Zornitza Stark Marked gene: AL117258.1 as ready
Mendeliome v0.11107 AL117258.1 Zornitza Stark Added comment: Comment when marking as ready: HGNC approved name is CIROP. Previous alias LMLN2.
Mendeliome v0.11107 AL117258.1 Zornitza Stark Gene: al117258.1 has been classified as Green List (High Evidence).
Mendeliome v0.11107 AL117258.1 Melanie Marty changed review comment from: Gene also known as CIROP

Homozygous or compound heterozygous CIROP variants identified in 12 families with congenital heart defects associated with heterotaxy.

Functional tests performed on Xenopus and zebrafish embryos showed that CIROP was essential for left side symmetry and is expressed in ciliated left–right organisers.
Sources: Literature; to: Gene also known as CIROP and LMLN2

Homozygous or compound heterozygous CIROP variants identified in 12 families with congenital heart defects associated with heterotaxy.

Functional tests performed on Xenopus and zebrafish embryos showed that CIROP was essential for left side symmetry and is expressed in ciliated left–right organisers.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4519 HIST1H4E Paul De Fazio gene: HIST1H4E was added
gene: HIST1H4E was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: HIST1H4E was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: HIST1H4E were set to 35202563
Phenotypes for gene: HIST1H4E were set to Neurodevelopmental disorder, HIST1H4E-related MONDO:0700092
Review for gene: HIST1H4E was set to GREEN
gene: HIST1H4E was marked as current diagnostic
Added comment: 17 patients identified with de novo missense variants affecting Lys31, Pro32, Arg35, Leu37, Arg40 (recurrent), Arg45 (recurrent), Tyr98 (recurrent). All individuals had ID/dev delay. Additional phenotypes in some but not all individuals included epilepsy, hypotonia, facial dysmorphism. Most had reduced birth length, OFC, weight (-1 to -3SD).
A zebrafish model has developmental defects.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4519 NRCAM Ee Ming Wong gene: NRCAM was added
gene: NRCAM was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: NRCAM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NRCAM were set to PMID: 35108495
Phenotypes for gene: NRCAM were set to neurodevelopmental disorder, MONDO:0700092
Penetrance for gene: NRCAM were set to unknown
Review for gene: NRCAM was set to GREEN
gene: NRCAM was marked as current diagnostic
Added comment: -Ten individuals from 8 families with developmental delay/intellectual disability, hypotonia, peripheral neuropathy, and/or spasticity
- Affected individuals are biallelic for missense and/or LoF variants which are mainly in the fibronectin type III (Fn-III) domain
- Zebrafish mutants lacking the third Fn-III domain displayed significantly altered swimming behavior compared to wild-type larvae (p < 0.03) and a trend toward increased amounts of alpha-tubulin fibers in the dorsal telencephalon, demonstrating an alteration in white matter tracts and projections
Sources: Literature
Mendeliome v0.11107 AL117258.1 Zornitza Stark Phenotypes for gene: AL117258.1 were changed from Heterotaxy, congenital heart defects to Heterotaxy MONDO:0018677, congenital heart defects
Mendeliome v0.11106 CPSF3 Alison Yeung Phenotypes for gene: CPSF3 were changed from Intellectual disability syndrome to Neurodevelopmental disorder, CPSF3-related, MONDO:0700092
Intellectual disability syndromic and non-syndromic v0.4519 HIST1H4D Paul De Fazio gene: HIST1H4D was added
gene: HIST1H4D was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: HIST1H4D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: HIST1H4D were set to 35202563
Phenotypes for gene: HIST1H4D were set to Neurodevelopmental disorder, HIST1H4D-related MONDO:0700092
Review for gene: HIST1H4D was set to AMBER
gene: HIST1H4D was marked as current diagnostic
Added comment: Single individual described with a de novo missense variant Arg41His (Arg40 in H4 nomenclature). Apart from langauge delay and moderate ID, phenotypes included facial dysmorphisms and cochlear abnormalities and arhinencephaly on MRI. Hearing was normal. Birth length, OFC, weight were all reduced (-2 to -2.5SD).
A zebrafish model has developmental defects.
Sources: Literature
Mendeliome v0.11105 CPSF3 Alison Yeung Classified gene: CPSF3 as Green List (high evidence)
Mendeliome v0.11105 CPSF3 Alison Yeung Gene: cpsf3 has been classified as Green List (High Evidence).
Mendeliome v0.11104 AL117258.1 Zornitza Stark Classified gene: AL117258.1 as Green List (high evidence)
Mendeliome v0.11104 AL117258.1 Zornitza Stark Gene: al117258.1 has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.100 ZBTB7A Daniel Flanagan gene: ZBTB7A was added
gene: ZBTB7A was added to Macrocephaly_Megalencephaly. Sources: Expert list
Mode of inheritance for gene: ZBTB7A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZBTB7A were set to 34515416; 31645653
Phenotypes for gene: ZBTB7A were set to Macrocephaly, neurodevelopmental delay, lymphoid hyperplasia, and persistent fetal hemoglobin (MIM#619769)
Review for gene: ZBTB7A was set to GREEN
Added comment: PMID: 34515416. Monoallelic ZBTB7A variants identified in 12 individuals from 11 families, with macrocephaly (11/12), some degree of ID (12/12), autistic features (7/12) and hypertrophy of pharyngeal lymphoid tissue (12/12). Variants included LoF variants and missense, 8 variants were de novo.

PMID: 31645653. De novo ZBTB7A missense identified in a boy with macrocephaly, intellectual disability, and sleep apnea.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.4519 CRLS1 Michelle Torres gene: CRLS1 was added
gene: CRLS1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CRLS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRLS1 were set to 35147173
Phenotypes for gene: CRLS1 were set to Mitochondrial disease MONDO:0044970 CRLS1-related
Added comment: - Three families (4 individuals) with cardiolipin deficiency.
- Two families (one consanguineous with 2 affected siblings) with homozygous the p.(Ile109Asn) had infantile progressive encephalopathy, bull’s eye maculopathy, auditory neuropathy, diabetes insipidus, autonomic instability, cardiac defects and early death.
- The fourth individual cHet p.(Ala172Asp) and p.(Leu217Phe) presented with chronic encephalopathy with neurodevelopmental regression, congenital nystagmus with decreased vision, sensorineural hearing loss, failure to thrive and acquired microcephaly.
- Functional studies on patient cells showed increased levels of the substrate of CRLS1 and impaired mitochondrial morphology and biogenesis
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4519 ZBTB7A Daniel Flanagan gene: ZBTB7A was added
gene: ZBTB7A was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: ZBTB7A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZBTB7A were set to 34515416; 31645653
Phenotypes for gene: ZBTB7A were set to Macrocephaly, neurodevelopmental delay, lymphoid hyperplasia, and persistent fetal hemoglobin (MIM#619769)
Review for gene: ZBTB7A was set to GREEN
Added comment: PMID: 34515416. Monoallelic ZBTB7A variants identified in 12 individuals from 11 families, with macrocephaly (11/12), some degree of ID (12/12), autistic features (7/12) and hypertrophy of pharyngeal lymphoid tissue (12/12). Variants included LoF variants and missense, 8 variants were de novo.

PMID: 31645653. De novo ZBTB7A missense identified in a boy with macrocephaly, intellectual disability, and sleep apnea.
Sources: Expert list
Mendeliome v0.11103 AL117258.1 Zornitza Stark Tag new gene name tag was added to gene: AL117258.1.
Intellectual disability syndromic and non-syndromic v0.4519 HIST1H4C Paul De Fazio reviewed gene: HIST1H4C: Rating: GREEN; Mode of pathogenicity: None; Publications: 35202563; Phenotypes: Tessadori-van Haaften neurodevelopmental syndrome 1 MIM#619758, Neurodevelopmental disorder, HIST1H4C-related MONDO:0700092; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mitochondrial disease v0.701 CRLS1 Michelle Torres gene: CRLS1 was added
gene: CRLS1 was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene: CRLS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRLS1 were set to 35147173
Phenotypes for gene: CRLS1 were set to Mitochondrial disease MONDO:0044970 CRLS1-related
Added comment: - Three families (4 individuals) with cardiolipin deficiency.
- Two families (one consanguineous with 2 affected siblings) with homozygous the p.(Ile109Asn) had infantile progressive encephalopathy, bull’s eye maculopathy, auditory neuropathy, diabetes insipidus, autonomic instability, cardiac defects and early death.
- The fourth individual cHet p.(Ala172Asp) and p.(Leu217Phe) presented with chronic encephalopathy with neurodevelopmental regression, congenital nystagmus with decreased vision, sensorineural hearing loss, failure to thrive and acquired microcephaly.
- Functional studies on patient cells showed increased levels of the substrate of CRLS1 and impaired mitochondrial morphology and biogenesis
Sources: Literature
Mendeliome v0.11103 HIST1H4F Zornitza Stark Marked gene: HIST1H4F as ready
Mendeliome v0.11103 HIST1H4F Zornitza Stark Gene: hist1h4f has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11103 HIST1H4E Paul De Fazio gene: HIST1H4E was added
gene: HIST1H4E was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HIST1H4E was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: HIST1H4E were set to 35202563
Phenotypes for gene: HIST1H4E were set to Neurodevelopmental disorder, HIST1H4E-related MONDO:0700092
Review for gene: HIST1H4E was set to GREEN
gene: HIST1H4E was marked as current diagnostic
Added comment: 17 patients identified with de novo missense variants affecting Lys31, Pro32, Arg35, Leu37, Arg40 (recurrent), Arg45 (recurrent), Tyr98 (recurrent). All individuals had ID/dev delay. Additional phenotypes in some but not all individuals included epilepsy, hypotonia, facial dysmorphism. Most had reduced birth length, OFC, weight (-1 to -3SD).
A zebrafish model has developmental defects.
Sources: Literature
Mendeliome v0.11103 HIST1H4D Paul De Fazio gene: HIST1H4D was added
gene: HIST1H4D was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HIST1H4D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: HIST1H4D were set to 35202563
Phenotypes for gene: HIST1H4D were set to Neurodevelopmental disorder, HIST1H4D-related MONDO:0700092
Review for gene: HIST1H4D was set to AMBER
gene: HIST1H4D was marked as current diagnostic
Added comment: Single individual described with a de novo missense variant Arg41His (Arg40 in H4 nomenclature). Apart from language delay and moderate ID, phenotypes included facial dysmorphisms and cochlear abnormalities and arhinencephaly on MRI. Hearing was normal. Birth length, OFC, weight were all reduced (-2 to -2.5SD).
A zebrafish model has developmental defects.
Sources: Literature
Mendeliome v0.11103 HIST1H4C Paul De Fazio edited their review of gene: HIST1H4C: Changed phenotypes: Tessadori-van Haaften neurodevelopmental syndrome 1 MIM#619758, Neurodevelopmental disorder, HIST1H4C related MONDO:0700092
Mendeliome v0.11103 HIST1H4C Paul De Fazio edited their review of gene: HIST1H4C: Changed phenotypes: Tessadori-van Haaften neurodevelopmental syndrome 1 MIM#619758, Neurodevelopmental disorder,HIST1H4C related MONDO:0700092
Mendeliome v0.11103 HIST1H4F Zornitza Stark Mode of inheritance for gene: HIST1H4F was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11102 HIST1H4F Zornitza Stark Phenotypes for gene: HIST1H4F were changed from Neurodevelopmental disorders to Neurodevelopmental disorder, MONDO:0700092, HIST1H4F-related
Mendeliome v0.11101 HIST1H4C Paul De Fazio reviewed gene: HIST1H4C: Rating: GREEN; Mode of pathogenicity: None; Publications: 35202563; Phenotypes: Tessadori-van Haaften neurodevelopmental syndrome 1 MIM#619758, Neurodevelopmental disorder MONDO:0700092; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.11101 HIST1H4F Zornitza Stark Classified gene: HIST1H4F as Amber List (moderate evidence)
Mendeliome v0.11101 HIST1H4F Zornitza Stark Gene: hist1h4f has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4519 HIST1H4F Zornitza Stark Marked gene: HIST1H4F as ready
Intellectual disability syndromic and non-syndromic v0.4519 HIST1H4F Zornitza Stark Gene: hist1h4f has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4519 HIST1H4F Zornitza Stark Phenotypes for gene: HIST1H4F were changed from Neurodevelopmental disorders to Neurodevelopmental disorder, MONDO:0700092, HIST1H4F-related
Mendeliome v0.11100 NRCAM Alison Yeung Phenotypes for gene: NRCAM were changed from neurodevelopmental disorder, MONDO:0700092 to neurodevelopmental disorder, NRCAM-related, MONDO:0700092
Intellectual disability syndromic and non-syndromic v0.4518 HIST1H4F Zornitza Stark Classified gene: HIST1H4F as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.4518 HIST1H4F Zornitza Stark Gene: hist1h4f has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4517 HIST1H4F Elena Savva edited their review of gene: HIST1H4F: Added comment: PMID: 35202563 - single de novo missense in a patient with neurodevelopmental features of intellectual disability and motor and/or gross developmental delay.
- zebrafish studies show a significant increase in all of mild dev delay, necrosis, defective organogenesis and pre-gastrulation failure
Sources: Literature; Changed rating: AMBER
Mendeliome v0.11099 CPSF3 Belinda Chong gene: CPSF3 was added
gene: CPSF3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CPSF3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPSF3 were set to 35121750
Phenotypes for gene: CPSF3 were set to Intellectual disability syndrome
Review for gene: CPSF3 was set to GREEN
Added comment: study of a deficit of observed homozygous carriers of missense variants, versus an expected number in a set of 153,054 chip-genotyped Icelanders, to identify potentially pathogenic genotypes

Six homozygous carriers of missense variants in CPSF3 show severe intellectual disability, seizures, microcephaly, and abnormal muscle tone.

- Four identified through Icelandic geneology (p.Gly468Glu), three carrier couples total of four children who had died prematurely. Tested archival samples for two of these children, and confirm a homozygous genotype.
- Two of Mexican descent (p.Ile354Thr), first-degree cousins
Sources: Literature
Mendeliome v0.11099 ZBTB11 Chern Lim reviewed gene: ZBTB11: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:35104841; Phenotypes: Intellectual developmental disorder, autosomal recessive 69 (MIM#618383), AR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.4517 ZBTB11 Chern Lim reviewed gene: ZBTB11: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:35104841; Phenotypes: Intellectual developmental disorder, autosomal recessive 69 (MIM#618383), AR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11099 NRCAM Alison Yeung Classified gene: NRCAM as Green List (high evidence)
Mendeliome v0.11099 NRCAM Alison Yeung Gene: nrcam has been classified as Green List (High Evidence).
Ataxia v0.326 ATP6V0A1 Zornitza Stark Marked gene: ATP6V0A1 as ready
Ataxia v0.326 ATP6V0A1 Zornitza Stark Gene: atp6v0a1 has been classified as Green List (High Evidence).
Mendeliome v0.11098 CRLS1 Zornitza Stark Marked gene: CRLS1 as ready
Mendeliome v0.11098 CRLS1 Zornitza Stark Gene: crls1 has been classified as Green List (High Evidence).
Mendeliome v0.11098 CRLS1 Zornitza Stark Classified gene: CRLS1 as Green List (high evidence)
Mendeliome v0.11098 CRLS1 Zornitza Stark Gene: crls1 has been classified as Green List (High Evidence).
Mendeliome v0.11097 CRLS1 Zornitza Stark reviewed gene: CRLS1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11097 AL117258.1 Melanie Marty gene: AL117258.1 was added
gene: AL117258.1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AL117258.1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AL117258.1 were set to 34903892
Phenotypes for gene: AL117258.1 were set to Heterotaxy, congenital heart defects
Review for gene: AL117258.1 was set to GREEN
Added comment: Gene also known as CIROP

Homozygous or compound heterozygous CIROP variants identified in 12 families with congenital heart defects associated with heterotaxy.

Functional tests performed on Xenopus and zebrafish embryos showed that CIROP was essential for left side symmetry and is expressed in ciliated left–right organisers.
Sources: Literature
Mendeliome v0.11097 NAV2 Alison Yeung Marked gene: NAV2 as ready
Mendeliome v0.11097 NAV2 Alison Yeung Added comment: Comment when marking as ready: Single reported individual. Functional studies and mouse model supportive evidence.
Mendeliome v0.11097 NAV2 Alison Yeung Gene: nav2 has been classified as Amber List (Moderate Evidence).
Ataxia v0.326 ATP6V0A1 Zornitza Stark Classified gene: ATP6V0A1 as Green List (high evidence)
Ataxia v0.326 ATP6V0A1 Zornitza Stark Gene: atp6v0a1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.120 Zornitza Stark removed gene:HIST1H4I from the panel
Mendeliome v0.11097 HIST1H4F Elena Savva gene: HIST1H4F was added
gene: HIST1H4F was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HIST1H4F was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: HIST1H4F were set to PMID: 35202563
Phenotypes for gene: HIST1H4F were set to Neurodevelopmental disorders
Review for gene: HIST1H4F was set to AMBER
Added comment: PMID: 35202563 - single de novo missense in a patient with neurodevelopmental features of intellectual disability and motor and/or gross developmental delay.
- zebrafish studies show a significant increase in all of mild dev delay, necrosis, defective organogenesis and pre-gastrulation failure
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4517 HIST1H4F Elena Savva gene: HIST1H4F was added
gene: HIST1H4F was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: HIST1H4F was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: HIST1H4F were set to PMID: 35202563
Phenotypes for gene: HIST1H4F were set to Neurodevelopmental disorders
Review for gene: HIST1H4F was set to GREEN
Added comment: PMID: 35202563 - single de novo missense in a patient with neurodevelopmental features of intellectual disability and motor and/or gross developmental delay.
- zebrafish studies show a significant increase in all of mild dev delay, necrosis, defective organogenesis and pre-gastrulation failure
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4517 HIST1H4I Zornitza Stark Marked gene: HIST1H4I as ready
Intellectual disability syndromic and non-syndromic v0.4517 HIST1H4I Zornitza Stark Gene: hist1h4i has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4517 HIST1H4I Zornitza Stark Phenotypes for gene: HIST1H4I were changed from Neurodevelopmental syndrome to Neurodevelopmental syndrome, MONDO:0700092, HIST1H4I-related
Intellectual disability syndromic and non-syndromic v0.4516 HIST1H4I Zornitza Stark Classified gene: HIST1H4I as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4516 HIST1H4I Zornitza Stark Gene: hist1h4i has been classified as Green List (High Evidence).
Mendeliome v0.11097 NAV2 Alison Yeung Classified gene: NAV2 as Amber List (moderate evidence)
Mendeliome v0.11097 NAV2 Alison Yeung Gene: nav2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11096 HIST1H4I Zornitza Stark Marked gene: HIST1H4I as ready
Mendeliome v0.11096 HIST1H4I Zornitza Stark Gene: hist1h4i has been classified as Green List (High Evidence).
Mendeliome v0.11096 HIST1H4I Zornitza Stark Phenotypes for gene: HIST1H4I were changed from Neurodevelopmental syndrome to Neurodevelopmental syndrome, MONDO:0700092, HIST1H4I-related
Mendeliome v0.11095 NRCAM Ee Ming Wong gene: NRCAM was added
gene: NRCAM was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NRCAM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NRCAM were set to PMID: 35108495
Phenotypes for gene: NRCAM were set to neurodevelopmental disorder, MONDO:0700092
Penetrance for gene: NRCAM were set to unknown
Review for gene: NRCAM was set to GREEN
gene: NRCAM was marked as current diagnostic
Added comment: -Ten individuals from 8 families with developmental delay/intellectual disability, hypotonia, peripheral neuropathy, and/or spasticity.
- Affected individuals are biallelic for missense and/or LoF variants which are mainly in the fibronectin type III (Fn-III) domain
- Zebrafish mutants lacking the third Fn-III domain displayed significantly altered swimming behavior compared to wild-type larvae (p < 0.03) and a trend toward increased amounts of alpha-tubulin fibers in the dorsal telencephalon, demonstrating an alteration in white matter tracts and projections
Sources: Literature
Mendeliome v0.11095 HIST1H4I Zornitza Stark Mode of inheritance for gene: HIST1H4I was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11094 HIST1H4I Zornitza Stark Classified gene: HIST1H4I as Green List (high evidence)
Mendeliome v0.11094 HIST1H4I Zornitza Stark Gene: hist1h4i has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1459 TIAM1 Alison Yeung Classified gene: TIAM1 as Green List (high evidence)
Genetic Epilepsy v0.1459 TIAM1 Alison Yeung Gene: tiam1 has been classified as Green List (High Evidence).
Mendeliome v0.11093 ZBTB7A Zornitza Stark Marked gene: ZBTB7A as ready
Mendeliome v0.11093 ZBTB7A Zornitza Stark Gene: zbtb7a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1458 TIAM1 Alison Yeung Classified gene: TIAM1 as Green List (high evidence)
Genetic Epilepsy v0.1458 TIAM1 Alison Yeung Gene: tiam1 has been classified as Green List (High Evidence).
Mendeliome v0.11093 ZBTB7A Zornitza Stark Classified gene: ZBTB7A as Green List (high evidence)
Mendeliome v0.11093 ZBTB7A Zornitza Stark Gene: zbtb7a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1458 TIAM1 Alison Yeung Classified gene: TIAM1 as Green List (high evidence)
Genetic Epilepsy v0.1458 TIAM1 Alison Yeung Gene: tiam1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1457 TIAM1 Alison Yeung Marked gene: TIAM1 as ready
Genetic Epilepsy v0.1457 TIAM1 Alison Yeung Gene: tiam1 has been classified as Red List (Low Evidence).
Mendeliome v0.11092 CRLS1 Michelle Torres gene: CRLS1 was added
gene: CRLS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CRLS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRLS1 were set to 35147173
Phenotypes for gene: CRLS1 were set to Mitochondrial disease MONDO:0044970 CRLS1-related
Added comment: - Three families (4 individuals) with cardiolipin deficiency.
- Two families (one consanguineous with 2 affected siblings) with homozygous the p.(Ile109Asn) had infantile progressive encephalopathy, bull’s eye maculopathy, auditory neuropathy, diabetes insipidus, autonomic instability, cardiac defects and early death.
- The fourth individual cHet p.(Ala172Asp) and p.(Leu217Phe) presented with chronic encephalopathy with neurodevelopmental regression, congenital nystagmus with decreased vision, sensorineural hearing loss, failure to thrive and acquired microcephaly.
- Functional studies on patient cells showed increased levels of the substrate of CRLS1 and impaired mitochondrial morphology and biogenesis
Sources: Literature
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.107 ROBO1 Zornitza Stark Phenotypes for gene: ROBO1 were changed from CAKUT to Syndromic disease, MONDO:0002254; CAKUT
Ataxia v0.325 ATP6V0A1 Chern Lim gene: ATP6V0A1 was added
gene: ATP6V0A1 was added to Ataxia - paediatric. Sources: Literature
Mode of inheritance for gene: ATP6V0A1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ATP6V0A1 were set to PMID:34909687
Phenotypes for gene: ATP6V0A1 were set to Neurodevelopmental disorder, MONDO:0700092, ATP6V0A1-associated
Review for gene: ATP6V0A1 was set to GREEN
gene: ATP6V0A1 was marked as current diagnostic
Added comment: PMID: 34909687
- 17 individuals from 14 unrelated families: 5 affected individuals with biallelic variants, presented with early-onset progressive myoclonus epilepsy with ataxia; 12 individuals carried de novo missense variants and showed severe developmental and epileptic encephalopathy.
- The mean age of onset was 11.8+/-7.5 years for individuals carrying the compound heterozygous variants and 5.8+/-4.2 months for individuals with the de novo variants.
- The R740Q variant, which alone accounts for ~50% of the mutations identified among our cases, leads to failure of lysosomal hydrolysis by directly impairing acidification of the endolysosomal compartment, causing autophagic dysfunction and severe developmental defect in C. elegans.
Sources: Literature
Genetic Epilepsy v0.1457 TIAM1 Alison Yeung gene: TIAM1 was added
gene: TIAM1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TIAM1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TIAM1 were set to Neurodevelopmental disorder, TIAM1-related, MONDO:0700092
Review for gene: TIAM1 was set to GREEN
Added comment: Reported in 4 unrelated individuals. Phenotype of developmental delay/intellectual disability and seizures. Loss of ortholog in Drosophila reduces the survival rate, and the surviving adults exhibit climbing defects, are prone to severe seizures, and have a short lifespan. Functional studies in 3 variants from two probands showed loss of function.
Sources: Literature
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.106 ROBO1 Zornitza Stark Marked gene: ROBO1 as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.106 ROBO1 Zornitza Stark Gene: robo1 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.106 ROBO1 Zornitza Stark Classified gene: ROBO1 as Green List (high evidence)
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.106 ROBO1 Zornitza Stark Gene: robo1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.119 HIST1H4I Elena Savva gene: HIST1H4I was added
gene: HIST1H4I was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: HIST1H4I was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: HIST1H4I were set to PMID: 35202563
Phenotypes for gene: HIST1H4I were set to Neurodevelopmental disorders
Review for gene: HIST1H4I was set to AMBER
Added comment: PMID: 35202563
- 3 unrelated de novo patients, p.His75Arg was recurring and observed in 2/3 probands.
- Zebrafish study shows both variants resulted in a significant increases in developmental issues such as in mild dev delay, necrosis and defective organogenesis.
- All patients had intellectual disability and motor and/or gross developmental delay and dysmorphisms.
- 2/3 patients showed bilateral conductive hearing loss
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4515 HIST1H4I Elena Savva gene: HIST1H4I was added
gene: HIST1H4I was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: HIST1H4I was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: HIST1H4I were set to PMID: 35202563
Phenotypes for gene: HIST1H4I were set to Neurodevelopmental syndrome
Review for gene: HIST1H4I was set to GREEN
Added comment: PMID: 35202563
- 3 unrelated de novo patients, p.His75Arg was recurring and observed in 2/3 probands.
- Zebrafish study shows both variants resulted in a significant increases in developmental issues such as in mild dev delay, necrosis and defective organogenesis.
- All patients had intellectual disability and motor and/or gross developmental delay and dysmorphisms.
- 2/3 patients showed bilateral conductive hearing loss
Sources: Literature
Genetic Epilepsy v0.1456 ATP6V0A1 Chern Lim gene: ATP6V0A1 was added
gene: ATP6V0A1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ATP6V0A1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ATP6V0A1 were set to PMID:34909687
Phenotypes for gene: ATP6V0A1 were set to Neurodevelopmental disorder, MONDO:0700092, ATP6V0A1-associated
Review for gene: ATP6V0A1 was set to GREEN
gene: ATP6V0A1 was marked as current diagnostic
Added comment: PMID: 34909687
- 17 individuals from 14 unrelated families: 5 affected individuals with biallelic variants, presented with early-onset progressive myoclonus epilepsy with ataxia; 12 individuals carried de novo missense variants and showed severe developmental and epileptic encephalopathy.
- The mean age of onset was 11.8+/-7.5 years for individuals carrying the compound heterozygous variants and 5.8+/-4.2 months for individuals with the de novo variants.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4515 TIAM1 Alison Yeung Marked gene: TIAM1 as ready
Intellectual disability syndromic and non-syndromic v0.4515 TIAM1 Alison Yeung Gene: tiam1 has been classified as Green List (High Evidence).
Mendeliome v0.11092 HIST1H4I Elena Savva gene: HIST1H4I was added
gene: HIST1H4I was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HIST1H4I was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: HIST1H4I were set to PMID: 35202563
Phenotypes for gene: HIST1H4I were set to Neurodevelopmental syndrome
Review for gene: HIST1H4I was set to GREEN
Added comment: PMID: 35202563
- 3 unrelated de novo patients, p.His75Arg was recurring and observed in 2/3 probands.
- Zebrafish study shows both variants resulted in a significant increases in developmental issues such as in mild dev delay, necrosis and defective organogenesis.
- All patients had intellectual disability and motor and/or gross developmental delay and dysmorphisms.
- 2/3 patients showed bilateral conductive hearing loss
Sources: Literature
Mendeliome v0.11092 NAV2 Dean Phelan gene: NAV2 was added
gene: NAV2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NAV2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAV2 were set to PMID:35218524
Phenotypes for gene: NAV2 were set to Developmental delay; cerebellar hypoplasia; cerebellar dysplasia
Review for gene: NAV2 was set to AMBER
Added comment: PMID:35218524
- Two compound heterozygous LOF variants identified in one female with developmental delay and a diagnosis of cerebellar hypoplasia and dysplasia. Functional studies showed cellular migration deficits. Hypomorphic mouse model revealed developmental anomalies including cerebellar hypoplasia and dysplasia, corpus callosum hypo-dysgenesis, and agenesis of the olfactory bulbs.
Sources: Literature
Mendeliome v0.11092 ZBTB7A Daniel Flanagan gene: ZBTB7A was added
gene: ZBTB7A was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ZBTB7A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZBTB7A were set to 34515416; 31645653
Phenotypes for gene: ZBTB7A were set to Macrocephaly, neurodevelopmental delay, lymphoid hyperplasia, and persistent fetal hemoglobin (MIM#619769)
Review for gene: ZBTB7A was set to GREEN
Added comment: PMID: 34515416. Monoallelic ZBTB7A variants identified in 12 individuals from 11 families, with macrocephaly (11/12), some degree of ID (12/12), autistic features (7/12) and hypertrophy of pharyngeal lymphoid tissue (12/12). Variants included LoF variants and missense, 8 variants were de novo.

PMID: 31645653. De novo ZBTB7A missense identified in a boy with macrocephaly, intellectual disability, and sleep apnea.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.4515 TIAM1 Alison Yeung Classified gene: TIAM1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4515 TIAM1 Alison Yeung Gene: tiam1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4514 ATP6V0A1 Zornitza Stark Marked gene: ATP6V0A1 as ready
Intellectual disability syndromic and non-syndromic v0.4514 ATP6V0A1 Zornitza Stark Gene: atp6v0a1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4514 ATP6V0A1 Zornitza Stark Phenotypes for gene: ATP6V0A1 were changed from Developmental disorder; Rett syndrome-like to Neurodevelopmental disorder, MONDO:0700092, ATP6V0A1-related
Intellectual disability syndromic and non-syndromic v0.4513 ATP6V0A1 Zornitza Stark Publications for gene: ATP6V0A1 were set to 30842224; 33057194
Mendeliome v0.11092 ATP6V0A1 Chern Lim edited their review of gene: ATP6V0A1: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11092 ATP6V0A1 Chern Lim reviewed gene: ATP6V0A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:34909687; Phenotypes: Neurodevelopmental disorder MONDO:0700092, ATP6V0A1-associated; Mode of inheritance: None; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.4512 ATP6V0A1 Zornitza Stark Mode of inheritance for gene: ATP6V0A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4511 TIAM1 Alison Yeung gene: TIAM1 was added
gene: TIAM1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: TIAM1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TIAM1 were set to Neurodevelopmental disorder, TIAM1-related, MONDO:0700092
Review for gene: TIAM1 was set to GREEN
Added comment: Reported in 4 unrelated individuals. Phenotype of developmental delay/intellectual disability and seizures. Loss of ortholog in Drosophila reduces the survival rate, and the surviving adults exhibit climbing defects, are prone to severe seizures, and have a short lifespan. Functional studies in 3 variants from two probands showed loss of function.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4511 ATP6V0A1 Zornitza Stark Classified gene: ATP6V0A1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4511 ATP6V0A1 Zornitza Stark Gene: atp6v0a1 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.105 ROBO1 Lucy Spencer gene: ROBO1 was added
gene: ROBO1 was added to Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic. Sources: Literature
Mode of inheritance for gene: ROBO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ROBO1 were set to PMID: 35227688
Phenotypes for gene: ROBO1 were set to CAKUT
Review for gene: ROBO1 was set to GREEN
Added comment: Six unrelated individuals with biallelic truncating or combined missense and truncating variants in ROBO1. Also another family with three affected fetal cases who also had biallelic ROBO1 variants. Pregnancies terminated at 17, 22 and 26 weeks due to a mix i symptoms including anamnios, kidney agenesis associated with ventriculomegaly, polycystic kidneys, and heart defects. Dysmorphic features were also found on fetal examination.

Kidney and genitourinary manifestations in other patients included unilateral or bilateral kidney agenesis, vesicoureteral junction obstruction, vesicoureteral reflux, posterior urethral valve, genital malformation, and increased kidney echogenicity
Sources: Literature
Mendeliome v0.11092 TIAM1 Alison Yeung Marked gene: TIAM1 as ready
Mendeliome v0.11092 TIAM1 Alison Yeung Gene: tiam1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4510 ATP6V0A1 Chern Lim reviewed gene: ATP6V0A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:34909687; Phenotypes: Early-onset progressive myoclonus epilepsy with ataxia, AR, severe developmental and epileptic encephalopathy, AD.; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Deafness_IsolatedAndComplex v1.119 EHD1 Zornitza Stark Marked gene: EHD1 as ready
Deafness_IsolatedAndComplex v1.119 EHD1 Zornitza Stark Gene: ehd1 has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v1.119 EHD1 Zornitza Stark Classified gene: EHD1 as Amber List (moderate evidence)
Deafness_IsolatedAndComplex v1.119 EHD1 Zornitza Stark Gene: ehd1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11092 TIAM1 Alison Yeung Classified gene: TIAM1 as Green List (high evidence)
Mendeliome v0.11092 TIAM1 Alison Yeung Gene: tiam1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.118 EHD1 Zornitza Stark gene: EHD1 was added
gene: EHD1 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: EHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EHD1 were set to 35149593
Phenotypes for gene: EHD1 were set to Inherited renal tubular disease, MONDO:0015962, EHD1-related
Review for gene: EHD1 was set to AMBER
Added comment: Six individuals (5-33 years) with proteinuria and a high-frequency hearing deficit reported with the homozygous missense variant c.1192C>T (p.R398W) in EHD1. Proteinuria (0.7-2.1 g/d) consisted predominantly of low molecular weight proteins, reflecting impaired renal proximal tubular endocytosis of filtered proteins. Ehd1 knockout and Ehd1R398W/R398W knockin mice also showed a high-frequency hearing deficit and impaired receptor-mediated endocytosis in proximal tubules, and a zebrafish model showed impaired ability to reabsorb low molecular weight dextran.

Single founder variant but two animal models, hence Amber
Sources: Literature
Mendeliome v0.11091 TIAM1 Alison Yeung gene: TIAM1 was added
gene: TIAM1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TIAM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TIAM1 were set to https://doi.org/10.1016/j.ajhg.2022.01.020
Phenotypes for gene: TIAM1 were set to Neurodevelopmental disorder, TIAM1-related, MONDO:0700092
Review for gene: TIAM1 was set to GREEN
Added comment: Reported in 4 unrelated individuals. Phenotype of developmental delay/intellectual disability and seizures. Loss of ortholog in Drosophila reduces the survival rate, and the surviving adults exhibit climbing defects, are prone to severe seizures, and have a short lifespan. Functional studies in 3 variants from two probands showed loss of function.
Sources: Literature
Mendeliome v0.11090 HIST1H4J Elena Savva reviewed gene: HIST1H4J: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 35202563, 31804630; Phenotypes: Neurodevelopmental syndrome, microcephaly, intellectual disability, dysmorphic features; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.11090 EHD1 Zornitza Stark Marked gene: EHD1 as ready
Mendeliome v0.11090 EHD1 Zornitza Stark Gene: ehd1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11090 EHD1 Zornitza Stark Classified gene: EHD1 as Amber List (moderate evidence)
Mendeliome v0.11090 EHD1 Zornitza Stark Gene: ehd1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11089 EHD1 Zornitza Stark gene: EHD1 was added
gene: EHD1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EHD1 were set to 35149593
Phenotypes for gene: EHD1 were set to Inherited renal tubular disease, MONDO:0015962, EHD1-related
Review for gene: EHD1 was set to AMBER
Added comment: Six individuals (5-33 years) with proteinuria and a high-frequency hearing deficit reported with the homozygous missense variant c.1192C>T (p.R398W) in EHD1. Proteinuria (0.7-2.1 g/d) consisted predominantly of low molecular weight proteins, reflecting impaired renal proximal tubular endocytosis of filtered proteins. Ehd1 knockout and Ehd1R398W/R398W knockin mice also showed a high-frequency hearing deficit and impaired receptor-mediated endocytosis in proximal tubules, and a zebrafish model showed impaired ability to reabsorb low molecular weight dextran. Single founder variant but two animal models, hence Amber
Sources: Literature
Proteinuria v0.174 EHD1 Zornitza Stark Marked gene: EHD1 as ready
Proteinuria v0.174 EHD1 Zornitza Stark Gene: ehd1 has been classified as Amber List (Moderate Evidence).
Proteinuria v0.174 EHD1 Zornitza Stark Classified gene: EHD1 as Amber List (moderate evidence)
Proteinuria v0.174 EHD1 Zornitza Stark Gene: ehd1 has been classified as Amber List (Moderate Evidence).
Proteinuria v0.173 EHD1 Zornitza Stark Marked gene: EHD1 as ready
Proteinuria v0.173 EHD1 Zornitza Stark Gene: ehd1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.4510 HIST1H4J Elena Savva reviewed gene: HIST1H4J: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 35202563, 31804630; Phenotypes: Neurodevelopmental syndrome, microcephaly, intellectual disability, dysmorphic features; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Proteinuria v0.173 EHD1 Zornitza Stark gene: EHD1 was added
gene: EHD1 was added to Proteinuria. Sources: Literature
Mode of inheritance for gene: EHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EHD1 were set to 35149593
Phenotypes for gene: EHD1 were set to Inherited renal tubular disease, MONDO:0015962, EHD1-related
Review for gene: EHD1 was set to AMBER
Added comment: Six individuals (5-33 years) with proteinuria and a high-frequency hearing deficit reported with the homozygous missense variant c.1192C>T (p.R398W) in EHD1. Proteinuria (0.7-2.1 g/d) consisted predominantly of low molecular weight proteins, reflecting impaired renal proximal tubular endocytosis of filtered proteins. Ehd1 knockout and Ehd1R398W/R398W knockin mice also showed a high-frequency hearing deficit and impaired receptor-mediated endocytosis in proximal tubules, and a zebrafish model showed impaired ability to reabsorb low molecular weight dextran.

Single founder variant but two animal models, hence Amber
Sources: Literature
Fetal anomalies v0.4686 SYNCRIP Zornitza Stark Marked gene: SYNCRIP as ready
Fetal anomalies v0.4686 SYNCRIP Zornitza Stark Gene: syncrip has been classified as Red List (Low Evidence).
Fetal anomalies v0.4686 SYNCRIP Zornitza Stark gene: SYNCRIP was added
gene: SYNCRIP was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: SYNCRIP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SYNCRIP were set to 34157790
Phenotypes for gene: SYNCRIP were set to SYNCRIP-related neurodevelopmental disorder
Review for gene: SYNCRIP was set to RED
Added comment: One of 8 individuals reported so far had PVNH. Other features present post-natally.
Sources: Expert Review
Fetal anomalies v0.4685 PIDD1 Zornitza Stark Classified gene: PIDD1 as Green List (high evidence)
Fetal anomalies v0.4685 PIDD1 Zornitza Stark Gene: pidd1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4684 PIDD1 Zornitza Stark reviewed gene: PIDD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pachygyria, Lissencephaly, Abnormality of the corpus callosum; Mode of inheritance: None
Fetal anomalies v0.4684 DEPDC5 Zornitza Stark Classified gene: DEPDC5 as Green List (high evidence)
Fetal anomalies v0.4684 DEPDC5 Zornitza Stark Gene: depdc5 has been classified as Green List (High Evidence).
Fetal anomalies v0.4683 DEPDC5 Zornitza Stark reviewed gene: DEPDC5: Rating: GREEN; Mode of pathogenicity: None; Publications: 31444548; Phenotypes: Epilepsy, familial focal, with variable foci 1 MIM#604364; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4683 AR Alison Yeung Phenotypes for gene: AR were changed from Androgen insensitivity, MIM# 300068 to Androgen insensitivity, MIM# 300068; Androgen insensitivity syndrome, MONDO:0019154
Fetal anomalies v0.4682 AR Alison Yeung reviewed gene: AR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Androgen insensitivity, MIM# 300068, Androgen insensitivity syndrome, MONDO:0019154; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v0.4682 AP4B1 Alison Yeung reviewed gene: AP4B1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 47, autosomal recessive, MIM# 614066; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4682 ANKS6 Alison Yeung reviewed gene: ANKS6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Nephronophthisis 16, MIM# 615382, MONDO:0014158; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4682 ANGPT2 Alison Yeung Phenotypes for gene: ANGPT2 were changed from Hydrops; Lymphatic malformation-10, MIM#619369 to Hydrops fetalis, MONDO:0015193; Lymphatic malformation-10, MIM#619369
Fetal anomalies v0.4681 ALDH1A2 Alison Yeung Phenotypes for gene: ALDH1A2 were changed from Congenital heart defects; diaphragmatic eventration; pulmonary hypoplasia; thymus aplasia to Multiple congenital anomalies, ALDH1A2-related, MONDO:0019042
Fetal anomalies v0.4679 ALB Alison Yeung Phenotypes for gene: ALB were changed from Analbuminemia- MIM#616000 to Analbuminemia, MIM#616000
Fetal anomalies v0.4678 ADGRG6 Alison Yeung Phenotypes for gene: ADGRG6 were changed from Lethal congenital contracture syndrome 9; OMIM #616503 to Lethal congenital contracture syndrome 9, OMIM #616503
Fetal anomalies v0.4677 ADAMTS19 Alison Yeung Phenotypes for gene: ADAMTS19 were changed from Heart valve disease (HVD) to Heart valve disorder, MONDO:0002869
Fetal anomalies v0.4676 PLK1 Zornitza Stark Marked gene: PLK1 as ready
Fetal anomalies v0.4676 PLK1 Zornitza Stark Gene: plk1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4676 PLK1 Zornitza Stark Classified gene: PLK1 as Amber List (moderate evidence)
Fetal anomalies v0.4676 PLK1 Zornitza Stark Gene: plk1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4675 PIGH Zornitza Stark Classified gene: PIGH as Green List (high evidence)
Fetal anomalies v0.4675 PIGH Zornitza Stark Gene: pigh has been classified as Green List (High Evidence).
Fetal anomalies v0.4674 PIGH Zornitza Stark reviewed gene: PIGH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Glycosylphosphatidylinositol biosynthesis defect 17, MIM# 618010; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4674 PIGH Zornitza Stark Marked gene: PIGH as ready
Fetal anomalies v0.4674 PIGH Zornitza Stark Gene: pigh has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4674 PIGH Zornitza Stark Classified gene: PIGH as Amber List (moderate evidence)
Fetal anomalies v0.4674 PIGH Zornitza Stark Gene: pigh has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4673 PHC1 Zornitza Stark Marked gene: PHC1 as ready
Fetal anomalies v0.4673 PHC1 Zornitza Stark Gene: phc1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4673 PHC1 Zornitza Stark Classified gene: PHC1 as Red List (low evidence)
Fetal anomalies v0.4673 PHC1 Zornitza Stark Gene: phc1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4672 ADAMTS17 Alison Yeung Phenotypes for gene: ADAMTS17 were changed from Weill-Marchesani 4 syndrome, recessive, 613195 to Weill-Marchesani 4 syndrome, recessive, MIM# 613195
Fetal anomalies v0.4671 PDCD6IP Zornitza Stark Marked gene: PDCD6IP as ready
Fetal anomalies v0.4671 PDCD6IP Zornitza Stark Gene: pdcd6ip has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4671 PDCD6IP Zornitza Stark Classified gene: PDCD6IP as Amber List (moderate evidence)
Fetal anomalies v0.4671 PDCD6IP Zornitza Stark Gene: pdcd6ip has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4670 PCYT2 Zornitza Stark Marked gene: PCYT2 as ready
Fetal anomalies v0.4670 PCYT2 Zornitza Stark Gene: pcyt2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4670 PCYT2 Zornitza Stark Classified gene: PCYT2 as Red List (low evidence)
Fetal anomalies v0.4670 PCYT2 Zornitza Stark Gene: pcyt2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4669 ACTC1 Alison Yeung Phenotypes for gene: ACTC1 were changed from Atrial septal defect 5 612794; Cardiomyopathy, hypertrophic, 11 612098 to Atrial septal defect 5, MIM# 612794; Cardiomyopathy, hypertrophic, 11 MIM# 612098
Fetal anomalies v0.4668 PCDH12 Zornitza Stark Marked gene: PCDH12 as ready
Fetal anomalies v0.4668 PCDH12 Zornitza Stark Gene: pcdh12 has been classified as Green List (High Evidence).
Fetal anomalies v0.4668 PCDH12 Zornitza Stark Classified gene: PCDH12 as Green List (high evidence)
Fetal anomalies v0.4668 PCDH12 Zornitza Stark Gene: pcdh12 has been classified as Green List (High Evidence).
Fetal anomalies v0.4667 PARP6 Zornitza Stark Marked gene: PARP6 as ready
Fetal anomalies v0.4667 PARP6 Zornitza Stark Gene: parp6 has been classified as Green List (High Evidence).
Fetal anomalies v0.4667 PARP6 Zornitza Stark Classified gene: PARP6 as Green List (high evidence)
Fetal anomalies v0.4667 PARP6 Zornitza Stark Gene: parp6 has been classified as Green List (High Evidence).
Fetal anomalies v0.4666 NKX2-5 Zornitza Stark Marked gene: NKX2-5 as ready
Fetal anomalies v0.4666 NKX2-5 Zornitza Stark Gene: nkx2-5 has been classified as Green List (High Evidence).
Fetal anomalies v0.4666 NKX2-5 Alison Yeung Marked gene: NKX2-5 as ready
Fetal anomalies v0.4666 NKX2-5 Alison Yeung Gene: nkx2-5 has been classified as Green List (High Evidence).
Fetal anomalies v0.4666 NKX2-5 Alison Yeung Phenotypes for gene: NKX2-5 were changed from CONGENITAL HYPOTHYROIDISM NON-GOITROUS TYPE 5; TETRALOGY OF FALLOT; ATRIAL SEPTAL DEFECT WITH ATRIOVENTRICULAR CONDUCTION DEFECTS to Atrial septal defect 7, with or without AV conduction defects, MIM# 108900; Hypoplastic left heart syndrome 2, MIM# 614435; Tetralogy of Fallot, MIM# 187500; Ventricular septal defect 3, MIM# 614432; Hypothyroidism, congenital nongoitrous, 5, MIM# 225250
Fetal anomalies v0.4665 NPC2 Zornitza Stark Marked gene: NPC2 as ready
Fetal anomalies v0.4665 NPC2 Zornitza Stark Gene: npc2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4665 NPC2 Zornitza Stark Phenotypes for gene: NPC2 were changed from NIEMANN-PICK DISEASE, TYPE C2 to Niemann-pick disease, type C2, MIM# 607625
Fetal anomalies v0.4664 NPC2 Zornitza Stark Publications for gene: NPC2 were set to
Fetal anomalies v0.4663 NPC2 Zornitza Stark Classified gene: NPC2 as Amber List (moderate evidence)
Fetal anomalies v0.4663 NPC2 Zornitza Stark Gene: npc2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4662 NPC2 Zornitza Stark edited their review of gene: NPC2: Changed rating: AMBER
Fetal anomalies v0.4662 NPHP1 Zornitza Stark Marked gene: NPHP1 as ready
Fetal anomalies v0.4662 NPHP1 Zornitza Stark Gene: nphp1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4662 NPHP1 Zornitza Stark Phenotypes for gene: NPHP1 were changed from NEPHRONOPHTHISIS TYPE 1; JOUBERT SYNDROME TYPE 4; SENIOR-LOKEN SYNDROME TYPE 1 to Joubert syndrome 4, MIM# 609583
Fetal anomalies v0.4661 NPHP1 Zornitza Stark Publications for gene: NPHP1 were set to
Fetal anomalies v0.4660 NKX2-5 Alison Yeung Publications for gene: NKX2-5 were set to
Fetal anomalies v0.4659 NKX2-5 Alison Yeung Mode of inheritance for gene: NKX2-5 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4658 NPHP3 Zornitza Stark Marked gene: NPHP3 as ready
Fetal anomalies v0.4658 NPHP3 Zornitza Stark Gene: nphp3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4658 NPHP3 Zornitza Stark Phenotypes for gene: NPHP3 were changed from RENAL-HEPATIC-PANCREATIC DYSPLASIA; NEPHRONOPHTHISIS TYPE 3; MECKEL SYNDROME TYPE 7 to Meckel syndrome 7, MIM# 267010; Nephronophthisis 3, MIM# 604387; Renal-hepatic-pancreatic dysplasia 1, MIM# 208540
Fetal anomalies v0.4657 NPHP3 Zornitza Stark Publications for gene: NPHP3 were set to
Fetal anomalies v0.4656 NIPBL Alison Yeung Marked gene: NIPBL as ready
Fetal anomalies v0.4656 NIPBL Alison Yeung Gene: nipbl has been classified as Green List (High Evidence).
Fetal anomalies v0.4656 NPHP3 Zornitza Stark edited their review of gene: NPHP3: Changed phenotypes: Meckel syndrome 7, MIM# 267010, Nephronophthisis 3, MIM# 604387, Renal-hepatic-pancreatic dysplasia 1, MIM# 208540
Fetal anomalies v0.4656 NIPBL Alison Yeung Phenotypes for gene: NIPBL were changed from CORNELIA DE LANGE SYNDROME TYPE 1 to Cornelia de Lange syndrome 1, MIM# 122470
Fetal anomalies v0.4655 NIPBL Alison Yeung Mode of inheritance for gene: NIPBL was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4654 NPHP3 Zornitza Stark edited their review of gene: NPHP3: Changed rating: GREEN
Fetal anomalies v0.4654 NIPBL Alison Yeung reviewed gene: NIPBL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cornelia de Lange syndrome 1, MIM# 122470; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4654 NPHP4 Zornitza Stark Marked gene: NPHP4 as ready
Fetal anomalies v0.4654 NPHP4 Zornitza Stark Gene: nphp4 has been classified as Green List (High Evidence).
Fetal anomalies v0.4654 NPHP4 Zornitza Stark Phenotypes for gene: NPHP4 were changed from NEPHRONOPHTHISIS TYPE 4 to Nephronophthisis 4, MIM# 606966; Senior-Loken syndrome 4, MIM# 606996
Fetal anomalies v0.4653 NPHP4 Zornitza Stark Publications for gene: NPHP4 were set to
Fetal anomalies v0.4652 NRAS Zornitza Stark Marked gene: NRAS as ready
Fetal anomalies v0.4652 NRAS Zornitza Stark Gene: nras has been classified as Green List (High Evidence).
Fetal anomalies v0.4652 NRAS Zornitza Stark Phenotypes for gene: NRAS were changed from NOONAN SYNDROME TYPE 6 to Noonan syndrome 6, MIM# 613224
Fetal anomalies v0.4651 NRAS Zornitza Stark Publications for gene: NRAS were set to
Fetal anomalies v0.4650 NRAS Zornitza Stark Mode of pathogenicity for gene: NRAS 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
Fetal anomalies v0.4649 NRAS Zornitza Stark Mode of inheritance for gene: NRAS was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4648 NSD1 Zornitza Stark Marked gene: NSD1 as ready
Fetal anomalies v0.4648 NSD1 Zornitza Stark Gene: nsd1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4648 NSD1 Zornitza Stark Phenotypes for gene: NSD1 were changed from BECKWITH-WIEDEMANN SYNDROME; WEAVER SYNDROME; SOTOS SYNDROME to Sotos syndrome 1, MIM# 117550
Fetal anomalies v0.4647 NSD1 Zornitza Stark Publications for gene: NSD1 were set to
Fetal anomalies v0.4646 NSD1 Zornitza Stark Mode of inheritance for gene: NSD1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4645 NSD1 Zornitza Stark Deleted their comment
Fetal anomalies v0.4645 NSD1 Zornitza Stark commented on gene: NSD1: Overgrowth, congenital anomalies.
Fetal anomalies v0.4645 NSD1 Zornitza Stark edited their review of gene: NSD1: Changed rating: GREEN
Fetal anomalies v0.4645 NSDHL Zornitza Stark Marked gene: NSDHL as ready
Fetal anomalies v0.4645 NSDHL Zornitza Stark Gene: nsdhl has been classified as Green List (High Evidence).
Fetal anomalies v0.4645 NSDHL Zornitza Stark Phenotypes for gene: NSDHL were changed from CK SYNDROME; CONGENITAL HEMIDYSPLASIA WITH ICHTHYOSIFORM ERYTHRODERMA AND LIMB DEFECTS to CK syndrome , MIM#300831
Fetal anomalies v0.4644 NSDHL Zornitza Stark Publications for gene: NSDHL were set to
Fetal anomalies v0.4643 NSDHL Zornitza Stark Mode of inheritance for gene: NSDHL 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
Fetal anomalies v0.4642 NSDHL Zornitza Stark reviewed gene: NSDHL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: CK syndrome , MIM#300831; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v0.4642 NUP107 Zornitza Stark Marked gene: NUP107 as ready
Fetal anomalies v0.4642 NUP107 Zornitza Stark Gene: nup107 has been classified as Green List (High Evidence).
Fetal anomalies v0.4642 NUP107 Zornitza Stark Phenotypes for gene: NUP107 were changed from EARLY-CHILDHOOD-ONSET STEROID-RESISTANT NEPHROTIC SYNDROME to Galloway-Mowat syndrome 7, MIM# 618348
Fetal anomalies v0.4641 NUP107 Zornitza Stark Publications for gene: NUP107 were set to
Fetal anomalies v0.4640 OCRL Zornitza Stark Marked gene: OCRL as ready
Fetal anomalies v0.4640 OCRL Zornitza Stark Gene: ocrl has been classified as Green List (High Evidence).
Fetal anomalies v0.4640 OFD1 Zornitza Stark Marked gene: OFD1 as ready
Fetal anomalies v0.4640 OFD1 Zornitza Stark Gene: ofd1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4640 OFD1 Zornitza Stark Phenotypes for gene: OFD1 were changed from SIMPSON-GOLABI-BEHMEL SYNDROME TYPE 2; JOUBERT SYNDROME TYPE 10; ORAL-FACIAL-DIGITAL SYNDROME TYPE 1 to Orofaciodigital syndrome I, MIM# 311200; Joubert syndrome 10, MIM# 300804
Fetal anomalies v0.4639 OFD1 Zornitza Stark changed review comment from: XLD. Polydactyly is a rare feature. Primarily facial/neurological features.; to: Well established gene-disease associations, multiple congenital anomalies.
Fetal anomalies v0.4639 OFD1 Zornitza Stark edited their review of gene: OFD1: Changed phenotypes: Orofaciodigital syndrome I, MIM# 311200, Joubert syndrome 10, MIM# 300804
Fetal anomalies v0.4639 OFD1 Zornitza Stark edited their review of gene: OFD1: Changed rating: GREEN; Changed phenotypes: Orofaciodigital syndrome I, MIM# 311200, Joubert syndrome 10 300804; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v0.4639 PCGF2 Zornitza Stark Marked gene: PCGF2 as ready
Fetal anomalies v0.4639 PCGF2 Zornitza Stark Gene: pcgf2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4639 PCGF2 Zornitza Stark Phenotypes for gene: PCGF2 were changed from Craniofacial Neurological Cardiovascular and Skeletal Features; Intellectual disability; INTELLECTUAL DUSBILITY to Turnpenny-Fry syndrome, MIM# 618371
Fetal anomalies v0.4638 PCGF2 Zornitza Stark Publications for gene: PCGF2 were set to 30526864
Fetal anomalies v0.4637 PCGF2 Zornitza Stark Mode of inheritance for gene: PCGF2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4636 PCNT Zornitza Stark Marked gene: PCNT as ready
Fetal anomalies v0.4636 PCNT Zornitza Stark Gene: pcnt has been classified as Green List (High Evidence).
Fetal anomalies v0.4636 PCNT Zornitza Stark Phenotypes for gene: PCNT were changed from MICROCEPHALIC OSTEODYSPLASTIC PRIMORDIAL DWARFISM, TYPE II to Microcephalic osteodysplastic primordial dwarfism, type II, MIM# 210720; MONDO:0008872
Fetal anomalies v0.4635 PCNT Zornitza Stark Publications for gene: PCNT were set to
Fetal anomalies v0.4634 PDHA1 Zornitza Stark Marked gene: PDHA1 as ready
Fetal anomalies v0.4634 PDHA1 Zornitza Stark Gene: pdha1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4634 PDHA1 Zornitza Stark Phenotypes for gene: PDHA1 were changed from X-LINKED LEIGH SYNDROME; PYRUVATE DEHYDROGENASE E1-ALPHA DEFICIENCY IN FEMALES; INTELLECTUAL DISABILTIY; Pyruvate dehydrogenase E1-alpha deficiency to Pyruvate dehydrogenase E1-alpha deficiency, MIM# 312170
Fetal anomalies v0.4633 PDHA1 Zornitza Stark Publications for gene: PDHA1 were set to 26865159
Fetal anomalies v0.4632 PDHA1 Zornitza Stark changed review comment from: Variants in this gene can cause congenital anomalies.
Sources: Literature; to: Variants in this gene can cause congenital anomalies, primarily affecting the brain. One report of CDH.
Sources: Literature
Fetal anomalies v0.4632 PDHA1 Zornitza Stark edited their review of gene: PDHA1: Changed publications: 33461977, 26865159
Fetal anomalies v0.4632 PDHA1 Zornitza Stark changed review comment from: Single individual reported as part of a cohort. Note variants in this gene can cause congenital anomalies.
Sources: Literature; to: Variants in this gene can cause congenital anomalies.
Sources: Literature
Fetal anomalies v0.4632 PDHA1 Zornitza Stark edited their review of gene: PDHA1: Changed rating: GREEN; Changed phenotypes: Pyruvate dehydrogenase E1-alpha deficiency, MIM# 312170
Fetal anomalies v0.4632 PEX1 Zornitza Stark Marked gene: PEX1 as ready
Fetal anomalies v0.4632 PEX1 Zornitza Stark Gene: pex1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4632 PEX1 Zornitza Stark Phenotypes for gene: PEX1 were changed from PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 1; INFANTILE REFSUM DISEASE; ADRENOLEUKODYSTROPHY NEONATAL to Peroxisome biogenesis disorder 1A (Zellweger) (MIM#214100)
Fetal anomalies v0.4631 PEX1 Zornitza Stark Publications for gene: PEX1 were set to
Fetal anomalies v0.4630 PEX10 Zornitza Stark Marked gene: PEX10 as ready
Fetal anomalies v0.4630 PEX10 Zornitza Stark Gene: pex10 has been classified as Green List (High Evidence).
Fetal anomalies v0.4630 PEX10 Zornitza Stark Phenotypes for gene: PEX10 were changed from ZELLWEGER SYNDROME; ADRENOLEUKODYSTROPHY NEONATAL; PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 7 to Peroxisome biogenesis disorder 6A (Zellweger), MIM# 614870
Fetal anomalies v0.4629 PEX10 Zornitza Stark Publications for gene: PEX10 were set to
Fetal anomalies v0.4628 PEX10 Zornitza Stark reviewed gene: PEX10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 6A (Zellweger), MIM# 614870; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4628 PEX11B Zornitza Stark Marked gene: PEX11B as ready
Fetal anomalies v0.4628 PEX11B Zornitza Stark Gene: pex11b has been classified as Green List (High Evidence).
Fetal anomalies v0.4628 PEX11B Zornitza Stark Phenotypes for gene: PEX11B were changed from Peroxisome biogenesis disorder 14B to Peroxisome biogenesis disorder 14B, MIM# 614920
Fetal anomalies v0.4627 PEX11B Zornitza Stark Publications for gene: PEX11B were set to
Fetal anomalies v0.4626 PEX11B Zornitza Stark changed review comment from: Congenital cataracts.; to: Congenital cataracts. Three families altogether, two published, and one internal.
Fetal anomalies v0.4626 PEX11B Zornitza Stark edited their review of gene: PEX11B: Changed rating: GREEN; Changed publications: 31724321
Fetal anomalies v0.4626 PEX11B Zornitza Stark edited their review of gene: PEX11B: Changed rating: AMBER
Fetal anomalies v0.4626 PEX11B Zornitza Stark edited their review of gene: PEX11B: Added comment: Congenital cataracts.; Changed rating: GREEN; Changed phenotypes: Peroxisome biogenesis disorder 14B, MIM# 614920; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4626 PEX12 Zornitza Stark Marked gene: PEX12 as ready
Fetal anomalies v0.4626 PEX12 Zornitza Stark Gene: pex12 has been classified as Green List (High Evidence).
Fetal anomalies v0.4626 PEX12 Zornitza Stark Phenotypes for gene: PEX12 were changed from ZELLWEGER SYNDROME; PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 3 to Peroxisome biogenesis disorder 3A (Zellweger), MIM# 614859
Fetal anomalies v0.4625 PEX12 Zornitza Stark Publications for gene: PEX12 were set to
Fetal anomalies v0.4624 PEX12 Zornitza Stark reviewed gene: PEX12: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 3A (Zellweger), MIM# 614859; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4624 PEX13 Zornitza Stark Marked gene: PEX13 as ready
Fetal anomalies v0.4624 PEX13 Zornitza Stark Gene: pex13 has been classified as Green List (High Evidence).
Fetal anomalies v0.4624 PEX13 Zornitza Stark Phenotypes for gene: PEX13 were changed from PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 13; ADRENOLEUKODYSTROPHY NEONATAL to Peroxisome biogenesis disorder 11A (Zellweger), MIM# 614883
Fetal anomalies v0.4623 PEX13 Zornitza Stark Publications for gene: PEX13 were set to
Fetal anomalies v0.4622 PEX13 Zornitza Stark reviewed gene: PEX13: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 11A (Zellweger), MIM# 614883; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4622 PEX14 Zornitza Stark Marked gene: PEX14 as ready
Fetal anomalies v0.4622 PEX14 Zornitza Stark Gene: pex14 has been classified as Green List (High Evidence).
Fetal anomalies v0.4622 PEX14 Zornitza Stark Phenotypes for gene: PEX14 were changed from ZELLWEGER SYNDROME; PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP K to Peroxisome biogenesis disorder 13A (Zellweger), MIM# 614887
Fetal anomalies v0.4621 PEX14 Zornitza Stark Publications for gene: PEX14 were set to
Fetal anomalies v0.4620 PEX14 Zornitza Stark reviewed gene: PEX14: Rating: GREEN; Mode of pathogenicity: None; Publications: 26627464; Phenotypes: Peroxisome biogenesis disorder 13A (Zellweger), MIM# 614887; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4620 PEX16 Zornitza Stark Marked gene: PEX16 as ready
Fetal anomalies v0.4620 PEX16 Zornitza Stark Gene: pex16 has been classified as Green List (High Evidence).
Fetal anomalies v0.4620 PEX16 Zornitza Stark Phenotypes for gene: PEX16 were changed from ZELLWEGER SYNDROME; PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 9 to Peroxisome biogenesis disorder 8A (Zellweger), MIM# 614876
Fetal anomalies v0.4619 PEX16 Zornitza Stark Publications for gene: PEX16 were set to
Fetal anomalies v0.4618 PEX16 Zornitza Stark reviewed gene: PEX16: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 8A (Zellweger), MIM# 614876; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4618 POMGNT1 Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association, congenital anomalies at the severe end of the spectrum.
Fetal anomalies v0.4618 POMGNT1 Zornitza Stark Marked gene: POMGNT1 as ready
Fetal anomalies v0.4618 POMGNT1 Zornitza Stark Gene: pomgnt1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4618 POMGNT1 Zornitza Stark Phenotypes for gene: POMGNT1 were changed from MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY LIMB-GIRDLE TYPE C3; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH MENTAL RETARDATION TYPE B3; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH BRAIN AND EYE ANOMALIES TYPE A3 (MDDGA3 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3, 253280
Fetal anomalies v0.4617 PEX19 Zornitza Stark Marked gene: PEX19 as ready
Fetal anomalies v0.4617 PEX19 Zornitza Stark Gene: pex19 has been classified as Green List (High Evidence).
Fetal anomalies v0.4617 PEX19 Zornitza Stark Phenotypes for gene: PEX19 were changed from ZELLWEGER SYNDROME; PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 14 to Peroxisome biogenesis disorder 12A (Zellweger), MIM# 614886
Fetal anomalies v0.4616 PEX19 Zornitza Stark Publications for gene: PEX19 were set to
Fetal anomalies v0.4615 PEX19 Zornitza Stark reviewed gene: PEX19: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 12A (Zellweger), MIM# 614886; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4615 PEX2 Zornitza Stark Marked gene: PEX2 as ready
Fetal anomalies v0.4615 PEX2 Zornitza Stark Gene: pex2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4615 PEX2 Zornitza Stark Phenotypes for gene: PEX2 were changed from ZELLWEGER SYNDROME; INFANTILE REFSUM DISEASE; PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 5 to Peroxisome biogenesis disorder 5A (Zellweger), MIM# 614866
Fetal anomalies v0.4614 PEX2 Zornitza Stark Publications for gene: PEX2 were set to
Fetal anomalies v0.4613 PEX2 Zornitza Stark reviewed gene: PEX2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 5A (Zellweger), MIM# 614866; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4613 PEX26 Zornitza Stark Marked gene: PEX26 as ready
Fetal anomalies v0.4613 PEX26 Zornitza Stark Gene: pex26 has been classified as Green List (High Evidence).
Fetal anomalies v0.4613 PEX26 Zornitza Stark Phenotypes for gene: PEX26 were changed from ZELLWEGER SYNDROME; PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 8; INFANTILE REFSUM DISEASE; ADRENOLEUKODYSTROPHY NEONATAL to Peroxisome biogenesis disorder 7A (Zellweger), MIM# 614872
Fetal anomalies v0.4612 PEX26 Zornitza Stark Publications for gene: PEX26 were set to
Fetal anomalies v0.4611 PEX26 Zornitza Stark reviewed gene: PEX26: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 7A (Zellweger), MIM# 614872; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4611 PEX3 Zornitza Stark Marked gene: PEX3 as ready
Fetal anomalies v0.4611 PEX3 Zornitza Stark Gene: pex3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4611 PEX3 Zornitza Stark Phenotypes for gene: PEX3 were changed from ZELLWEGER SYNDROME; PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 12 to Peroxisome biogenesis disorder 10A (Zellweger), MIM# 614882
Fetal anomalies v0.4610 PEX3 Zornitza Stark Publications for gene: PEX3 were set to
Fetal anomalies v0.4609 PEX3 Zornitza Stark reviewed gene: PEX3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 10A (Zellweger), MIM# 614882; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4609 PEX5 Zornitza Stark Marked gene: PEX5 as ready
Fetal anomalies v0.4609 PEX5 Zornitza Stark Gene: pex5 has been classified as Green List (High Evidence).
Fetal anomalies v0.4609 PEX5 Zornitza Stark Phenotypes for gene: PEX5 were changed from ZELLWEGER SYNDROME; INFANTILE REFSUM DISEASE; ADRENOLEUKODYSTROPHY NEONATAL to Peroxisome biogenesis disorder 2A (Zellweger), MIM# 214110
Fetal anomalies v0.4608 PEX5 Zornitza Stark Publications for gene: PEX5 were set to
Fetal anomalies v0.4607 PEX5 Zornitza Stark reviewed gene: PEX5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 2A (Zellweger), MIM# 214110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4607 NR2F2 Zornitza Stark Marked gene: NR2F2 as ready
Fetal anomalies v0.4607 NR2F2 Zornitza Stark Gene: nr2f2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4607 NR2F2 Zornitza Stark Phenotypes for gene: NR2F2 were changed from CONGENITAL HEART DEFECTS, MULTIPLE TYPES, 4 to Congenital heart defects, multiple types, 4, MIM# 615779
Fetal anomalies v0.4606 NR2F2 Zornitza Stark Publications for gene: NR2F2 were set to
Fetal anomalies v0.4605 NR2F2 Zornitza Stark Mode of inheritance for gene: NR2F2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4604 PEX6 Zornitza Stark Marked gene: PEX6 as ready
Fetal anomalies v0.4604 PEX6 Zornitza Stark Gene: pex6 has been classified as Green List (High Evidence).
Fetal anomalies v0.4604 PEX6 Zornitza Stark Phenotypes for gene: PEX6 were changed from ZELLWEGER SYNDROME; PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 4 to Peroxisome biogenesis disorder 4A (Zellweger) (MIM#614862)
Fetal anomalies v0.4603 PEX6 Zornitza Stark Publications for gene: PEX6 were set to
Fetal anomalies v0.4602 PGAP2 Zornitza Stark Marked gene: PGAP2 as ready
Fetal anomalies v0.4602 PGAP2 Zornitza Stark Gene: pgap2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4602 PGAP2 Zornitza Stark Phenotypes for gene: PGAP2 were changed from INTELLECTUAL DISABILITY to Hyperphosphatasia with mental retardation syndrome 3, MIM# 614207, MONDO:0013628
Fetal anomalies v0.4601 PGAP2 Zornitza Stark Publications for gene: PGAP2 were set to
Fetal anomalies v0.4600 PGAP2 Zornitza Stark changed review comment from: Bi-allelic variants in this gene are typically associated with severe DD/ID, hypotonia with very poor motor development, poor speech, and increased serum alkaline phosphatase, although presentations with milder ID have also been reported. More than 10 unrelated families reported.; to: Bi-allelic variants in this gene are typically associated with severe DD/ID, hypotonia with very poor motor development, poor speech, and increased serum alkaline phosphatase, although presentations with milder ID have also been reported. More than 10 unrelated families reported.

Microcephaly is a feature.
Fetal anomalies v0.4600 PGAP3 Zornitza Stark Marked gene: PGAP3 as ready
Fetal anomalies v0.4600 PGAP3 Zornitza Stark Gene: pgap3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4600 PGAP3 Zornitza Stark Phenotypes for gene: PGAP3 were changed from HYPERPHOSPHATASIA WITH MENTAL RETARDATION SYNDROME 4 to Hyperphosphatasia with mental retardation syndrome 4, MIM# 615716, MONDO:0014318
Fetal anomalies v0.4599 PGAP3 Zornitza Stark Publications for gene: PGAP3 were set to
Fetal anomalies v0.4598 PGAP3 Zornitza Stark changed review comment from: Bi-allelic variants in this gene are associated with severe DD/ID, lack of speech acquisition, seizures, and dysmorphic facial features. Laboratory studies show increased serum alkaline phosphatase. More than 15 unrelated families reported.; to: Bi-allelic variants in this gene are associated with severe DD/ID, lack of speech acquisition, seizures, and dysmorphic facial features. Laboratory studies show increased serum alkaline phosphatase. More than 15 unrelated families reported.

Microcephaly, CC abnormalities reported.
Fetal anomalies v0.4598 PGM1 Zornitza Stark Marked gene: PGM1 as ready
Fetal anomalies v0.4598 PGM1 Zornitza Stark Gene: pgm1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4598 PGM1 Zornitza Stark Phenotypes for gene: PGM1 were changed from CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IT to Congenital disorder of glycosylation, type It 614921
Fetal anomalies v0.4597 PGM1 Zornitza Stark Publications for gene: PGM1 were set to
Fetal anomalies v0.4596 PGM1 Zornitza Stark changed review comment from: The most common features include cleft lip and bifid uvula, apparent at birth, followed by hepatopathy, intermittent hypoglycemia, short stature, and exercise intolerance, often accompanied by increased serum creatine kinase. Less common features include rhabdomyolysis, dilated cardiomyopathy, and hypogonadotropic hypogonadism; to: Over 50 individuals reported. The most common features include cleft lip and bifid uvula, apparent at birth, followed by hepatopathy, intermittent hypoglycemia, short stature, and exercise intolerance, often accompanied by increased serum creatine kinase. Less common features include rhabdomyolysis, dilated cardiomyopathy, and hypogonadotropic hypogonadism
Fetal anomalies v0.4596 PGM1 Zornitza Stark edited their review of gene: PGM1: Changed publications: 24499211, 33342467
Fetal anomalies v0.4596 PGM1 Zornitza Stark commented on gene: PGM1: The most common features include cleft lip and bifid uvula, apparent at birth, followed by hepatopathy, intermittent hypoglycemia, short stature, and exercise intolerance, often accompanied by increased serum creatine kinase. Less common features include rhabdomyolysis, dilated cardiomyopathy, and hypogonadotropic hypogonadism
Fetal anomalies v0.4596 PHF8 Zornitza Stark Marked gene: PHF8 as ready
Fetal anomalies v0.4596 PHF8 Zornitza Stark Gene: phf8 has been classified as Green List (High Evidence).
Fetal anomalies v0.4596 PHF8 Zornitza Stark Phenotypes for gene: PHF8 were changed from MENTAL RETARDATION SYNDROMIC X-LINKED SIDERIUS TYPE to Intellectual developmental disorder, X-linked, syndromic, Siderius type, MIM# 300263
Fetal anomalies v0.4595 PHF8 Zornitza Stark Publications for gene: PHF8 were set to
Fetal anomalies v0.4594 PHF8 Zornitza Stark commented on gene: PHF8: Cleft lip/palate is a feature.
Fetal anomalies v0.4594 PHF8 Zornitza Stark edited their review of gene: PHF8: Changed phenotypes: Intellectual developmental disorder, X-linked, syndromic, Siderius type, MIM# 300263
Fetal anomalies v0.4594 PHGDH Zornitza Stark Marked gene: PHGDH as ready
Fetal anomalies v0.4594 PHGDH Zornitza Stark Gene: phgdh has been classified as Green List (High Evidence).
Fetal anomalies v0.4594 PHGDH Zornitza Stark Phenotypes for gene: PHGDH were changed from PHOSPHOGLYCERATE DEHYDROGENASE DEFICIENCY; NEU-LAXOVA SYNDROME to Neu-Laxova syndrome 1, MIM# 256520
Fetal anomalies v0.4593 PHGDH Zornitza Stark Publications for gene: PHGDH were set to
Fetal anomalies v0.4592 PHIP Zornitza Stark Marked gene: PHIP as ready
Fetal anomalies v0.4592 PHIP Zornitza Stark Gene: phip has been classified as Red List (Low Evidence).
Fetal anomalies v0.4592 PHIP Zornitza Stark Phenotypes for gene: PHIP were changed from Developmental delay, ID, obesity and dysmorphic features to Chung-Jansen syndrome, MIM#617991
Fetal anomalies v0.4591 PHIP Zornitza Stark Publications for gene: PHIP were set to
Fetal anomalies v0.4590 PHIP Zornitza Stark Mode of inheritance for gene: PHIP was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4589 PHIP Zornitza Stark Classified gene: PHIP as Red List (low evidence)
Fetal anomalies v0.4589 PHIP Zornitza Stark Gene: phip has been classified as Red List (Low Evidence).
Fetal anomalies v0.4588 PHIP Zornitza Stark changed review comment from: Recent large case series describing 20 individuals; variable expressivity, some inherited from mildly affected parents, most de novo.
Sources: Expert list; to: Recent large case series describing 20 individuals; variable expressivity, some inherited from mildly affected parents, most de novo. ID, dysmorphism and obesity are the key features. Clinical presentation is typically post-natal.
Sources: Expert list
Fetal anomalies v0.4588 PHIP Zornitza Stark edited their review of gene: PHIP: Changed rating: RED
Fetal anomalies v0.4588 PIEZO2 Zornitza Stark Marked gene: PIEZO2 as ready
Fetal anomalies v0.4588 PIEZO2 Zornitza Stark Gene: piezo2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4588 PIEZO2 Zornitza Stark Phenotypes for gene: PIEZO2 were changed from Ataxia, dysmetria, contractures & scoliosis with normal cognition but loss of discriminative touch perception; ARTHROGRYPOSIS, DISTAL, TYPE 3 to Marden-Walker syndrome, MIM# 248700; Arthrogryposis, distal, type 3, MIM# 114300
Fetal anomalies v0.4587 PIEZO2 Zornitza Stark Publications for gene: PIEZO2 were set to
Fetal anomalies v0.4586 PIEZO2 Zornitza Stark Mode of inheritance for gene: PIEZO2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.4585 PIEZO2 Zornitza Stark changed review comment from: Gene is associated with several phenotypes. The other two DA phenotypes do not have ID as a feature. Mild ID is part of the phenotype of some individuals with DA type 3. ID is part of the phenotype of Marden-Walker, however only one individual with PIEZO2 variant has been reported to date.; to: Gene is associated with several phenotypes, contractures are a key feature.
Fetal anomalies v0.4585 PIEZO2 Zornitza Stark edited their review of gene: PIEZO2: Changed rating: GREEN
Fetal anomalies v0.4585 PIGA Zornitza Stark Marked gene: PIGA as ready
Fetal anomalies v0.4585 PIGA Zornitza Stark Gene: piga has been classified as Green List (High Evidence).
Fetal anomalies v0.4585 PIGA Zornitza Stark Phenotypes for gene: PIGA were changed from MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME 2 to Multiple congenital anomalies-hypotonia-seizures syndrome 2, MIM#300868
Fetal anomalies v0.4584 PIGA Zornitza Stark Publications for gene: PIGA were set to
Fetal anomalies v0.4583 PIGL Zornitza Stark Marked gene: PIGL as ready
Fetal anomalies v0.4583 PIGL Zornitza Stark Gene: pigl has been classified as Green List (High Evidence).
Fetal anomalies v0.4583 PIGL Zornitza Stark Phenotypes for gene: PIGL were changed from ZUNICH NEUROECTODERMAL SYNDROME to CHIME syndrome, MIM# 280000, MONDO:0010221
Fetal anomalies v0.4582 PIGL Zornitza Stark Publications for gene: PIGL were set to
Fetal anomalies v0.4581 PIGL Zornitza Stark Tag SV/CNV tag was added to gene: PIGL.
Fetal anomalies v0.4581 PIGO Zornitza Stark Marked gene: PIGO as ready
Fetal anomalies v0.4581 PIGO Zornitza Stark Gene: pigo has been classified as Green List (High Evidence).
Fetal anomalies v0.4581 PIGO Zornitza Stark Phenotypes for gene: PIGO were changed from HYPERPHOSPHATASIA WITH MENTAL RETARDATION SYNDROME 2 to Hyperphosphatasia with mental retardation syndrome 2, MIM# 614749, MONDO:0013882
Fetal anomalies v0.4580 PIGO Zornitza Stark Publications for gene: PIGO were set to
Fetal anomalies v0.4579 PIGT Zornitza Stark Marked gene: PIGT as ready
Fetal anomalies v0.4579 PIGT Zornitza Stark Gene: pigt has been classified as Green List (High Evidence).
Fetal anomalies v0.4579 PIGT Zornitza Stark Phenotypes for gene: PIGT were changed from MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME 3 to Multiple congenital anomalies-hypotonia-seizures syndrome 3, MIM# 615398, MONDO:0014165
Fetal anomalies v0.4578 PIGT Zornitza Stark Publications for gene: PIGT were set to
Fetal anomalies v0.4577 PIGV Zornitza Stark Marked gene: PIGV as ready
Fetal anomalies v0.4577 PIGV Zornitza Stark Gene: pigv has been classified as Green List (High Evidence).
Fetal anomalies v0.4577 PIGV Zornitza Stark Phenotypes for gene: PIGV were changed from HYPERPHOSPHATASIA WITH MENTAL RETARDATION to Hyperphosphatasia with mental retardation syndrome 1, MIM# 239300, MONDO:0009398
Fetal anomalies v0.4576 PIGV Zornitza Stark Publications for gene: PIGV were set to
Fetal anomalies v0.4575 PIK3CA Zornitza Stark Marked gene: PIK3CA as ready
Fetal anomalies v0.4575 PIK3CA Zornitza Stark Gene: pik3ca has been classified as Green List (High Evidence).
Fetal anomalies v0.4575 PIK3CA Zornitza Stark Phenotypes for gene: PIK3CA were changed from CLOVES: CONGENITAL LIPOMATOUS OVERGROWTH, VASCULAR MALFORMATIONS, AND EPIDERMAL NEVI; HEMIMEGALENCEPHALY PIK3CA; MEGALENCEPHALY-CAPILLARY MALFORMATION-POLYMICROGYRIA SYNDROME, SOMATIC 3 to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2, MIM# 615937
Fetal anomalies v0.4574 PIK3CA Zornitza Stark Publications for gene: PIK3CA were set to 30712880; 28425981
Fetal anomalies v0.4573 PIK3CA Zornitza Stark Mode of inheritance for gene: PIK3CA was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4572 PIK3CA Zornitza Stark changed review comment from: Single case report of MCAP with fetal hydrops presentation, PIK3CA variant identified.
Sources: Expert list; to: Multiple congenital anomalies.
Sources: Expert list
Fetal anomalies v0.4572 PIK3CA Zornitza Stark edited their review of gene: PIK3CA: Changed rating: GREEN; Changed phenotypes: Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2, MIM# 615937
Fetal anomalies v0.4572 PIK3R1 Zornitza Stark Marked gene: PIK3R1 as ready
Fetal anomalies v0.4572 PIK3R1 Zornitza Stark Gene: pik3r1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4572 PIK3R1 Zornitza Stark Phenotypes for gene: PIK3R1 were changed from AGAMMAGLOBULINEMIA 7, AUTOSOMAL RECESSIVE; SHORT SYNDROME to SHORT syndrome, MIM#269880
Fetal anomalies v0.4571 PIK3R1 Zornitza Stark changed review comment from: ID is not part of the phenotype.; to: IUGR.
Fetal anomalies v0.4571 PIK3R1 Zornitza Stark edited their review of gene: PIK3R1: Changed rating: GREEN
Vitreoretinopathy v1.2 COL9A3 Ain Roesley changed review comment from: In family 2 with missense Gly130Ser, ther is 228 hets 0 homs in gnomAD v2.

This leaves 1 family with the splice variant which is absent in gnomAD, cDNA studies to prove a splice defect and segregation in 14 affecteds across 2 generations; to: In family 2 with missense Gly130Ser, there is 228 hets 0 homs in gnomAD v2.

This leaves 1 family with the splice variant which is absent in gnomAD, cDNA studies to prove a splice defect and segregation in 14 affecteds across 2 generations
Vitreoretinopathy v1.2 COL9A3 Ain Roesley reviewed gene: COL9A3: Rating: AMBER; Mode of pathogenicity: None; Publications: 33633367; Phenotypes: Peripheral vitreoretinal degeneration and retinal detachment, AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Fetal anomalies v0.4571 PIK3R2 Zornitza Stark Marked gene: PIK3R2 as ready
Fetal anomalies v0.4571 PIK3R2 Zornitza Stark Gene: pik3r2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4571 PIK3R2 Zornitza Stark Phenotypes for gene: PIK3R2 were changed from MEGALENCEPHALY-POLYMICROGYRIA-POLYDACTYLY-HYDROCEPHALUS SYNDROME 1 to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, MIM# 603387
Fetal anomalies v0.4570 PIK3R2 Zornitza Stark Publications for gene: PIK3R2 were set to 28425981
Fetal anomalies v0.4569 PIK3R2 Zornitza Stark Mode of inheritance for gene: PIK3R2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4568 PITX3 Zornitza Stark Marked gene: PITX3 as ready
Fetal anomalies v0.4568 PITX3 Zornitza Stark Gene: pitx3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4568 PITX3 Zornitza Stark Phenotypes for gene: PITX3 were changed from CATARACT AUTOSOMAL DOMINANT; ANTERIOR SEGMENT MESENCHYMAL DYSGENESIS; CATARACT POSTERIOR POLAR TYPE 4 to Anterior segment dysgenesis 1, multiple subtypes, MIM# 107250; Cataract 11, multiple types, MIM# 610623; Microphthalmia
Fetal anomalies v0.4567 PITX3 Zornitza Stark Publications for gene: PITX3 were set to
Fetal anomalies v0.4566 PITX3 Zornitza Stark Mode of inheritance for gene: PITX3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4565 PKD1L1 Zornitza Stark Marked gene: PKD1L1 as ready
Fetal anomalies v0.4565 PKD1L1 Zornitza Stark Gene: pkd1l1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4565 PKD1L1 Zornitza Stark Phenotypes for gene: PKD1L1 were changed from Laterality defects to Heterotaxy, visceral, 8, autosomal (MIM#617205)
Fetal anomalies v0.4564 PKD1L1 Zornitza Stark Publications for gene: PKD1L1 were set to
Fetal anomalies v0.4563 PKHD1 Zornitza Stark Marked gene: PKHD1 as ready
Fetal anomalies v0.4563 PKHD1 Zornitza Stark Gene: pkhd1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4563 PKHD1 Zornitza Stark Phenotypes for gene: PKHD1 were changed from POLYCYSTIC KIDNEY DISEASE, AUTOSOMAL RECESSIVE to Polycystic kidney disease 4, with or without hepatic disease, MIM# 263200
Fetal anomalies v0.4562 PKHD1 Zornitza Stark changed review comment from: Included due to possible phenotypic overlap.
Sources: Expert Review; to: Presents antenatally.
Sources: Expert Review
Fetal anomalies v0.4562 PKLR Zornitza Stark Marked gene: PKLR as ready
Fetal anomalies v0.4562 PKLR Zornitza Stark Gene: pklr has been classified as Green List (High Evidence).
Fetal anomalies v0.4562 PKLR Zornitza Stark Publications for gene: PKLR were set to
Fetal anomalies v0.4561 PMM2 Zornitza Stark Marked gene: PMM2 as ready
Fetal anomalies v0.4561 PMM2 Zornitza Stark Gene: pmm2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4561 PMM2 Zornitza Stark Phenotypes for gene: PMM2 were changed from CONGENITAL DISORDERS OF GLYCOSYLATION to Congenital disorder of glycosylation, type Ia , MIM#212065
Fetal anomalies v0.4560 PMM2 Zornitza Stark Publications for gene: PMM2 were set to
Fetal anomalies v0.4559 PMM2 Zornitza Stark reviewed gene: PMM2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type Ia , MIM#212065; Mode of inheritance: None
Fetal anomalies v0.4559 PNKP Zornitza Stark Marked gene: PNKP as ready
Fetal anomalies v0.4559 PNKP Zornitza Stark Gene: pnkp has been classified as Green List (High Evidence).
Fetal anomalies v0.4559 PNKP Zornitza Stark Phenotypes for gene: PNKP were changed from ATAXIA-OCULOMOTOR APRAXIA 4; EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 10 to Microcephaly, seizures, and developmental delay, MIM#613402
Fetal anomalies v0.4558 PNKP Zornitza Stark Publications for gene: PNKP were set to
Fetal anomalies v0.4557 POC1A Zornitza Stark Marked gene: POC1A as ready
Fetal anomalies v0.4557 POC1A Zornitza Stark Gene: poc1a has been classified as Green List (High Evidence).
Fetal anomalies v0.4557 POC1A Zornitza Stark Phenotypes for gene: POC1A were changed from PRIMORDIAL DWARFISM; SHORT STATURE, ONYCHODYSPLASIA, FACIAL DYSMORPHISM, AND HYPOTRICHOSIS SYNDROME to Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis, MIM#614813
Fetal anomalies v0.4556 POC1A Zornitza Stark changed review comment from: ID is not a prominent feature of the phenotype.; to: Skeletal dysplasia.
Fetal anomalies v0.4556 POC1A Zornitza Stark edited their review of gene: POC1A: Changed rating: GREEN
Fetal anomalies v0.4556 POGZ Zornitza Stark Marked gene: POGZ as ready
Fetal anomalies v0.4556 POGZ Zornitza Stark Gene: pogz has been classified as Green List (High Evidence).
Fetal anomalies v0.4556 POGZ Zornitza Stark Phenotypes for gene: POGZ were changed from INTELLECTUAL DISABILITY to White-Sutton syndrome, MIM# 616364; MONDO:0014606
Fetal anomalies v0.4555 POGZ Zornitza Stark Publications for gene: POGZ were set to
Fetal anomalies v0.4554 PLK1 Belinda Chong gene: PLK1 was added
gene: PLK1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PLK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLK1 were set to 33875846
Phenotypes for gene: PLK1 were set to Epilepsy; microcephaly; intellectual disability
Review for gene: PLK1 was set to AMBER
gene: PLK1 was marked as current diagnostic
Added comment: Five individuals reported with microcephaly. However, unclear if microcephaly is pre or post natal.
Sources: Literature
Fetal anomalies v0.4554 POGZ Zornitza Stark Mode of inheritance for gene: POGZ was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4553 POGZ Zornitza Stark changed review comment from: White-Sutton syndrome is a neurodevelopmental disorder characterized by delayed psychomotor development apparent in infancy and a characteristic constellation of dysmorphic facial features. Additional features may include hypotonia, sensorineural hearing impairment, visual defects, joint laxity, and gastrointestinal difficulties, such as poor feeding.

More than 40 individuals reported.; to: White-Sutton syndrome is a neurodevelopmental disorder characterized by delayed psychomotor development apparent in infancy and a characteristic constellation of dysmorphic facial features. Additional features may include hypotonia, sensorineural hearing impairment, visual defects, joint laxity, and gastrointestinal difficulties, such as poor feeding.

More than 40 individuals reported.

Microcephaly is a feature, congenital heart disease rarely reported.
Fetal anomalies v0.4553 POLR1C Zornitza Stark Marked gene: POLR1C as ready
Fetal anomalies v0.4553 POLR1C Zornitza Stark Gene: polr1c has been classified as Green List (High Evidence).
Fetal anomalies v0.4553 POLR1C Zornitza Stark Phenotypes for gene: POLR1C were changed from TREACHER COLLINS SYNDROME TYPE 3 to Treacher Collins syndrome 3, MIM# 248390
Fetal anomalies v0.4552 POLR1C Zornitza Stark Publications for gene: POLR1C were set to
Fetal anomalies v0.4551 POLR1C Zornitza Stark changed review comment from: 8 unrelated individuals reported, ID is part of the phenotype.
Sources: Expert list; to: Treacher Collins more likely to be detected antenatally.

Sources: Expert list
Fetal anomalies v0.4551 POLR1C Zornitza Stark edited their review of gene: POLR1C: Changed phenotypes: Leukodystrophy, hypomyelinating, 11, MIM# 616494, Treacher Collins syndrome 3, MIM# 248390
Fetal anomalies v0.4551 POMGNT2 Zornitza Stark Marked gene: POMGNT2 as ready
Fetal anomalies v0.4551 POMGNT2 Zornitza Stark Gene: pomgnt2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4551 POMGNT2 Zornitza Stark Phenotypes for gene: POMGNT2 were changed from WALKER WARBERG SYNDROME to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 8, MIM# 614830
Fetal anomalies v0.4550 POMGNT2 Zornitza Stark edited their review of gene: POMGNT2: Changed phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 8 614830
Fetal anomalies v0.4550 POMK Zornitza Stark Marked gene: POMK as ready
Fetal anomalies v0.4550 POMK Zornitza Stark Gene: pomk has been classified as Green List (High Evidence).
Fetal anomalies v0.4550 POMT1 Zornitza Stark Marked gene: POMT1 as ready
Fetal anomalies v0.4550 POMT1 Zornitza Stark Gene: pomt1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4550 POMT1 Zornitza Stark Phenotypes for gene: POMT1 were changed from MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY LIMB-GIRDLE TYPE C1; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH MENTAL RETARDATION TYPE B1; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH BRAIN AND EYE ANOMALIES TYPE A1 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 236670; Walker-Walburg syndrome
Fetal anomalies v0.4549 POMT1 Zornitza Stark Publications for gene: POMT1 were set to
Fetal anomalies v0.4548 POMT2 Zornitza Stark Marked gene: POMT2 as ready
Fetal anomalies v0.4548 POMT2 Zornitza Stark Gene: pomt2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4548 POMT2 Zornitza Stark Phenotypes for gene: POMT2 were changed from MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH BRAIN AND EYE ANOMALIES TYPE A2; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH MENTAL RETARDATION TYPE B2; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY LIMB-GIRDLE TYPE C2 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2 613150
Fetal anomalies v0.4547 POMT2 Zornitza Stark Publications for gene: POMT2 were set to
Fetal anomalies v0.4546 POMT2 Zornitza Stark edited their review of gene: POMT2: Changed phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2 613150
Fetal anomalies v0.4546 POMT2 Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association, multiple anomalies at the more severe end of the spectrum.
Fetal anomalies v0.4546 PIGH Belinda Chong gene: PIGH was added
gene: PIGH was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PIGH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGH were set to 29573052; 33156547; 29603516
Phenotypes for gene: PIGH were set to Glycosylphosphatidylinositol biosynthesis defect 17, MIM# 618010
Review for gene: PIGH was set to AMBER
gene: PIGH was marked as current diagnostic
Added comment: Microcephaly appears to present at postnatal in these individuals.

Three further families reported, including two sibs with microcephaly.
Sources: Literature
Fetal anomalies v0.4546 PHC1 Belinda Chong gene: PHC1 was added
gene: PHC1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PHC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PHC1 were set to 23418308
Phenotypes for gene: PHC1 were set to Microcephaly 11, primary, autosomal recessive, MIM#615414
Review for gene: PHC1 was set to RED
gene: PHC1 was marked as current diagnostic
Added comment: Short stature and microcephaly, currently not enough information.

Single family reported with functional data.
Sources: Literature
Fetal anomalies v0.4546 POR Zornitza Stark Marked gene: POR as ready
Fetal anomalies v0.4546 POR Zornitza Stark Gene: por has been classified as Green List (High Evidence).
Fetal anomalies v0.4546 PORCN Zornitza Stark Marked gene: PORCN as ready
Fetal anomalies v0.4546 PORCN Zornitza Stark Gene: porcn has been classified as Green List (High Evidence).
Fetal anomalies v0.4546 PORCN Zornitza Stark Phenotypes for gene: PORCN were changed from FOCAL DERMAL HYPOPLASIA to Focal dermal hypoplasia, MIM# 305600
Fetal anomalies v0.4545 PORCN Zornitza Stark Publications for gene: PORCN were set to
Fetal anomalies v0.4544 POU1F1 Zornitza Stark Marked gene: POU1F1 as ready
Fetal anomalies v0.4544 POU1F1 Zornitza Stark Gene: pou1f1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4544 POU1F1 Zornitza Stark Phenotypes for gene: POU1F1 were changed from POU1F1-RELATED COMBINED PITUITARY HORMONE DEFICIENCY to Pituitary hormone deficiency, combined, 1, MIM# 613038
Fetal anomalies v0.4543 POU1F1 Zornitza Stark Publications for gene: POU1F1 were set to
Fetal anomalies v0.4542 POU1F1 Zornitza Stark changed review comment from: Hypotonia with untreated hypothyroidism, not truly ID.; to: Presentation with hydrops reported.
Fetal anomalies v0.4542 POU1F1 Zornitza Stark edited their review of gene: POU1F1: Changed rating: GREEN; Changed publications: 7593413
Fetal anomalies v0.4542 PPP2R1A Zornitza Stark Marked gene: PPP2R1A as ready
Fetal anomalies v0.4542 PPP2R1A Zornitza Stark Gene: ppp2r1a has been classified as Green List (High Evidence).
Fetal anomalies v0.4542 PPP2R1A Zornitza Stark Phenotypes for gene: PPP2R1A were changed from INTELLECTUAL DISABILITY to Mental retardation, autosomal dominant 36, MIM#616362; Microcephaly-corpus callosum hypoplasia-intellectual disability-facial dysmorphism syndrome, MONDO:0014605
Fetal anomalies v0.4541 PPP2R1A Zornitza Stark Publications for gene: PPP2R1A were set to
Fetal anomalies v0.4540 PPP2R1A Zornitza Stark Mode of pathogenicity for gene: PPP2R1A was changed from to Other
Fetal anomalies v0.4539 PPP2R1A Zornitza Stark Mode of inheritance for gene: PPP2R1A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4538 PPP2R5D Zornitza Stark Marked gene: PPP2R5D as ready
Fetal anomalies v0.4538 PPP2R5D Zornitza Stark Gene: ppp2r5d has been classified as Green List (High Evidence).
Fetal anomalies v0.4538 PPP2R5D Zornitza Stark Phenotypes for gene: PPP2R5D were changed from INTELLECTUAL DISABILITY to Mental retardation, autosomal dominant 35, MIM#616355
Fetal anomalies v0.4537 PPP2R5D Zornitza Stark Publications for gene: PPP2R5D were set to
Fetal anomalies v0.4536 PPP2R5D Zornitza Stark Mode of inheritance for gene: PPP2R5D was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4535 PPP2R5D Zornitza Stark changed review comment from: (P/LP in ClinVar): >15 missense, 1 PTC DN missense mechanism suspected: Functional studies showed defective holoenzyme assembly in transfected HEK293 cells and mutant subunits hindering dephosphorylation of B56δ-anchored substrates. Moreover,. p.P53S was the only variant to not show defective binding - authors speculate an alternative mechanism. Unknown mechanism for PTCs: pLI = 1 and very few in gnomAD. Missense variants cluster p.198-207 (Decipher).; to: (P/LP in ClinVar): >15 missense, 1 PTC DN missense mechanism suspected: Functional studies showed defective holoenzyme assembly in transfected HEK293 cells and mutant subunits hindering dephosphorylation of B56δ-anchored substrates. Moreover,. p.P53S was the only variant to not show defective binding - authors speculate an alternative mechanism. Unknown mechanism for PTCs: pLI = 1 and very few in gnomAD. Missense variants cluster p.198-207 (Decipher).

Hydrocephalus reported in some.
Fetal anomalies v0.4535 PPP1CB Zornitza Stark Marked gene: PPP1CB as ready
Fetal anomalies v0.4535 PPP1CB Zornitza Stark Gene: ppp1cb has been classified as Green List (High Evidence).
Fetal anomalies v0.4535 PPP1CB Zornitza Stark Phenotypes for gene: PPP1CB were changed from Rasopathy with developmental delay, short stature and sparse slow-growing hair to Noonan syndrome-like disorder with loose anlagen hair 2, OMIM # 617506
Fetal anomalies v0.4534 PPP1CB Zornitza Stark Publications for gene: PPP1CB were set to
Fetal anomalies v0.4533 PPP1CB Zornitza Stark Mode of inheritance for gene: PPP1CB was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4532 PDCD6IP Belinda Chong gene: PDCD6IP was added
gene: PDCD6IP was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PDCD6IP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDCD6IP were set to 32286682
Phenotypes for gene: PDCD6IP were set to Primary microcephaly
Review for gene: PDCD6IP was set to AMBER
gene: PDCD6IP was marked as current diagnostic
Added comment: Primary microcephaly was noticed at birth and their occipital-frontal circumference (OFC) was ≤−2 standard deviations (SD), may be relevant for this panel however, currently not enough information.

One consanguineous family with 2 affected sibs with primary microcephaly (-4SD), intellectual disability and short stature (-5/6SD), and homozygous frameshift variant in PDCD6IP. The homozygous variant was confirmed in both affected sibs, while the four healthy siblings and parents were heterozygous. The clinical features observed in the patients were similar to the phenotypes observed in mouse and zebrafish models of PDCD6IP mutations in previous studies.
Sources: Literature
Fetal anomalies v0.4532 PCYT2 Belinda Chong gene: PCYT2 was added
gene: PCYT2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PCYT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCYT2 were set to 31637422
Phenotypes for gene: PCYT2 were set to Spastic paraplegia 82, autosomal recessive MIM#618770
Review for gene: PCYT2 was set to RED
gene: PCYT2 was marked as current diagnostic
Added comment: Brain imaging shows progressive cerebral and cerebellar atrophy however, normal initially.

5 individuals from 4 families reported with progressive neurologic disorder characterized by global developmental delay apparent from infancy, significant motor impairment, and progressive spasticity mainly affecting the lower limbs. Some never achieved walking, whereas others lost the ability to walk or walk with an unsteady gait. Additional features included variably impaired intellectual development with language difficulties, ocular anomalies, such as nystagmus and visual impairment, and seizures. Brain imaging shows progressive cerebral and cerebellar atrophy, as well as white matter hyperintensities. Overall poor growth, but only one individual reported with microcephaly -3SD, and head size appears relatively spared against other reported growth parameters.
Sources: Literature
Fetal anomalies v0.4532 PCDH12 Belinda Chong gene: PCDH12 was added
gene: PCDH12 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PCDH12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCDH12 were set to 27164683; 30178464
Phenotypes for gene: PCDH12 were set to Diencephalic-mesencephalic junction dysplasia syndrome 1, MIM# 251280
Review for gene: PCDH12 was set to GREEN
gene: PCDH12 was marked as current diagnostic
Added comment: Brain malformations were detectable antenatally.

Diencephalic-mesencephalic junction dysplasia syndrome-1 (DMJDS1) is an autosomal recessive neurodevelopmental disorder characterized by progressive microcephaly, severely delayed or even absent psychomotor development with profound intellectual disability, and spasticity or dystonia. Some patients may have seizures and/or visual impairment. Brain imaging shows a characteristic developmental malformation of the midbrain; subtle intracranial calcifications may also be present. At least 12 families reported.
Sources: Literature
Fetal anomalies v0.4532 PARP6 Belinda Chong gene: PARP6 was added
gene: PARP6 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PARP6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PARP6 were set to 34067418
Phenotypes for gene: PARP6 were set to Intellectual disability; Epilepsy; Microcephaly
Review for gene: PARP6 was set to GREEN
gene: PARP6 was marked as current diagnostic
Added comment: IUGR and partial agenesis of the corpus callosum has been observed.

Four unrelated individuals reported with de novo variants in this gene and a neurodevelopmental phenotype. Supportive functional data. One pair of siblings with a homozygous missense: limited evidence for bi-allelic variants causing disease.
Sources: Literature
Mendeliome v0.11088 IL6ST Zornitza Stark Phenotypes for gene: IL6ST were changed from Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523; Stuve-Wiedemann syndrome 2, MIM# 619751: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response; Hyper-IgE syndrome, autosomal dominant; Immunodeficiency 94 with autoinflammation and dysmorphic facies, MIM# 619750 to Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523; Stuve-Wiedemann syndrome 2, MIM# 619751: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response; Hyper-IgE recurrent infection syndrome 4A, autosomal dominant, MIM# 619752; Immunodeficiency 94 with autoinflammation and dysmorphic facies, MIM# 619750
Autoinflammatory Disorders v0.131 IL6ST Zornitza Stark Marked gene: IL6ST as ready
Autoinflammatory Disorders v0.131 IL6ST Zornitza Stark Gene: il6st has been classified as Red List (Low Evidence).
Autoinflammatory Disorders v0.131 IL6ST Zornitza Stark gene: IL6ST was added
gene: IL6ST was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: IL6ST was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IL6ST were set to 33517393
Phenotypes for gene: IL6ST were set to Immunodeficiency 94 with autoinflammation and dysmorphic facies 619750
Review for gene: IL6ST was set to RED
Added comment: PMID: 33517393 - Materna-Kiryluk et al 2021 - describe a patient with a novel syndrome of neonatal onset immunodeficiency with autoinflammation and dysmorphic features. The patient was found using exome sequencing to have a de novo IL6ST Tyr186_Tyr190del variant, which was present as a mosaic. It was found in around 15–40% of cells depending on the tissue (blood, urine sediment, hair bulbs and buccal swab).
Sources: Literature
Mendeliome v0.11087 IL6ST Zornitza Stark Phenotypes for gene: IL6ST were changed from Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523; Stuve-Wiedemann syndrome 2, MIM# 619751: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response; Hyper-IgE syndrome, autosomal dominant to Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523; Stuve-Wiedemann syndrome 2, MIM# 619751: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response; Hyper-IgE syndrome, autosomal dominant; Immunodeficiency 94 with autoinflammation and dysmorphic facies, MIM# 619750
Mendeliome v0.11086 IL6ST Zornitza Stark edited their review of gene: IL6ST: Changed phenotypes: Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523, Stuve-Wiedemann syndrome 2, MIM# 619751: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response, Hyper-IgE syndrome, autosomal dominant, Immunodeficiency 94 with autoinflammation and dysmorphic facies, MIM# 619750
Fetal anomalies v0.4532 PUF60 Zornitza Stark commented on gene: PUF60: Multiple congenital anomalies.
Fetal anomalies v0.4532 PSAP Zornitza Stark Phenotypes for gene: PSAP were changed from Combined SAP deficiency, MIM# 611721; Encephalopathy due to prosaposin deficiency, MONDO:0012719; Krabbe disease, atypical, MIM# 611722, MONDO:0012720; Metachromatic leukodystrophy due to SAP-b deficiency, MIM# 249900, MONDO:0009590; Gaucher disease, atypical, MIM# 610539, MONDO:0012517 to Combined SAP deficiency, MIM# 611721
Fetal anomalies v0.4531 PSAP Zornitza Stark edited their review of gene: PSAP: Added comment: Hepatosplenomegaly at birth at the most severe end of the spectrum.; Changed rating: AMBER; Changed phenotypes: Combined SAP deficiency, MIM# 611721
Fetal anomalies v0.4531 PSAP Zornitza Stark Deleted their comment
Fetal anomalies v0.4531 TBC1D7 Zornitza Stark Marked gene: TBC1D7 as ready
Fetal anomalies v0.4531 TBC1D7 Zornitza Stark Gene: tbc1d7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4531 TBC1D7 Zornitza Stark Classified gene: TBC1D7 as Amber List (moderate evidence)
Fetal anomalies v0.4531 TBC1D7 Zornitza Stark Gene: tbc1d7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4530 TAOK1 Zornitza Stark Marked gene: TAOK1 as ready
Fetal anomalies v0.4530 TAOK1 Zornitza Stark Gene: taok1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4530 TAOK1 Zornitza Stark Classified gene: TAOK1 as Green List (high evidence)
Fetal anomalies v0.4530 TAOK1 Zornitza Stark Gene: taok1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4529 STT3A Zornitza Stark Marked gene: STT3A as ready
Fetal anomalies v0.4529 STT3A Zornitza Stark Gene: stt3a has been classified as Green List (High Evidence).
Fetal anomalies v0.4529 STT3A Zornitza Stark Classified gene: STT3A as Green List (high evidence)
Fetal anomalies v0.4529 STT3A Zornitza Stark Gene: stt3a has been classified as Green List (High Evidence).
Fetal anomalies v0.4528 RHEB Zornitza Stark Marked gene: RHEB as ready
Fetal anomalies v0.4528 RHEB Zornitza Stark Gene: rheb has been classified as Green List (High Evidence).
Fetal anomalies v0.4528 RHEB Zornitza Stark Classified gene: RHEB as Green List (high evidence)
Fetal anomalies v0.4528 RHEB Zornitza Stark Gene: rheb has been classified as Green List (High Evidence).
Fetal anomalies v0.4527 PPP2R5C Zornitza Stark Marked gene: PPP2R5C as ready
Fetal anomalies v0.4527 PPP2R5C Zornitza Stark Gene: ppp2r5c has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4527 PPP2R5C Zornitza Stark Classified gene: PPP2R5C as Amber List (moderate evidence)
Fetal anomalies v0.4527 PPP2R5C Zornitza Stark Gene: ppp2r5c has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4526 LMNB2 Zornitza Stark Marked gene: LMNB2 as ready
Fetal anomalies v0.4526 LMNB2 Zornitza Stark Gene: lmnb2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4526 LMNB2 Zornitza Stark Classified gene: LMNB2 as Green List (high evidence)
Fetal anomalies v0.4526 LMNB2 Zornitza Stark Gene: lmnb2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4525 MCM7 Zornitza Stark Marked gene: MCM7 as ready
Fetal anomalies v0.4525 MCM7 Zornitza Stark Gene: mcm7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4525 MCM7 Zornitza Stark Classified gene: MCM7 as Amber List (moderate evidence)
Fetal anomalies v0.4525 MCM7 Zornitza Stark Gene: mcm7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4524 LMNB1 Zornitza Stark Marked gene: LMNB1 as ready
Fetal anomalies v0.4524 LMNB1 Zornitza Stark Gene: lmnb1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4524 LMNB1 Zornitza Stark Classified gene: LMNB1 as Green List (high evidence)
Fetal anomalies v0.4524 LMNB1 Zornitza Stark Gene: lmnb1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4523 LINGO1 Zornitza Stark Marked gene: LINGO1 as ready
Fetal anomalies v0.4523 LINGO1 Zornitza Stark Gene: lingo1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4523 LINGO1 Zornitza Stark Classified gene: LINGO1 as Amber List (moderate evidence)
Fetal anomalies v0.4523 LINGO1 Zornitza Stark Gene: lingo1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4522 LAGE3 Zornitza Stark Marked gene: LAGE3 as ready
Fetal anomalies v0.4522 LAGE3 Zornitza Stark Gene: lage3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4522 LAGE3 Zornitza Stark Classified gene: LAGE3 as Green List (high evidence)
Fetal anomalies v0.4522 LAGE3 Zornitza Stark Gene: lage3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4521 KIF21B Zornitza Stark Marked gene: KIF21B as ready
Fetal anomalies v0.4521 KIF21B Zornitza Stark Gene: kif21b has been classified as Green List (High Evidence).
Fetal anomalies v0.4521 KIF21B Zornitza Stark Phenotypes for gene: KIF21B were changed from Global developmental delay; Intellectual disability; Abnormality of brain morphology; Microcephaly to Neurodevelopmental disorder, MONDO:0700092; Global developmental delay; Intellectual disability; Abnormality of brain morphology; Microcephaly
Fetal anomalies v0.4520 KIF21B Zornitza Stark Classified gene: KIF21B as Green List (high evidence)
Fetal anomalies v0.4520 KIF21B Zornitza Stark Gene: kif21b has been classified as Green List (High Evidence).
Fetal anomalies v0.4519 PQBP1 Zornitza Stark Marked gene: PQBP1 as ready
Fetal anomalies v0.4519 PQBP1 Zornitza Stark Gene: pqbp1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4519 PQBP1 Zornitza Stark Phenotypes for gene: PQBP1 were changed from RENPENNING S(YNDROME 1 to Renpenning syndrome, MIM#309500
Fetal anomalies v0.4518 PQBP1 Zornitza Stark Publications for gene: PQBP1 were set to
Fetal anomalies v0.4517 PRKAR1A Zornitza Stark Marked gene: PRKAR1A as ready
Fetal anomalies v0.4517 PRKAR1A Zornitza Stark Gene: prkar1a has been classified as Green List (High Evidence).
Fetal anomalies v0.4517 PRKAR1A Zornitza Stark Phenotypes for gene: PRKAR1A were changed from ACRODYSOSTOSIS to Acrodysostosis 1, with or without hormone resistance, MIM#101800
Fetal anomalies v0.4516 PRKAR1A Zornitza Stark Mode of inheritance for gene: PRKAR1A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4515 PRKAR1A Zornitza Stark changed review comment from: Multiple phenotypes associated with this gene, but this particular OMIM condition has ID as part of the phenotype.; to: Multiple phenotypes associated with this gene, but this particular OMIM condition has prenatal growth retardation as part of the phenotype.
Fetal anomalies v0.4515 PRKD1 Zornitza Stark Marked gene: PRKD1 as ready
Fetal anomalies v0.4515 PRKD1 Zornitza Stark Gene: prkd1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4515 PRKD1 Zornitza Stark Phenotypes for gene: PRKD1 were changed from Syndromic congenital heart defects to Congenital heart defects and ectodermal dysplasia, MIM#617364
Fetal anomalies v0.4514 PRKD1 Zornitza Stark Mode of inheritance for gene: PRKD1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.4513 PRKD1 Zornitza Stark edited their review of gene: PRKD1: Added comment: PMID: 27479907 (2016): three individuals reported, two with the c.1774G>A variant and one with the c.896T>G variant. All had congenital heart disease, two had some developmental delay, and two had variable features of ectodermal dysplasia, including sparse hair, dry skin, thin skin, fragile nails, premature loss of primary teeth, and small widely spaced teeth; the third individuals had a 'disorganized eyebrow.'

PMID: 32817298 (2020) - Two additional unrelated cases with de novo variants, c.1774G>C and c.1808G>A, and telangiectasia, ectodermal dysplasia, brachydactyly and congenital heart disease. Functional analysis using in vitro kinase assays with recombinant proteins showed that the c.1808G>A, p.(Arg603His) variant represents a gain-of-function mutation encoding an enzyme with a constitutive, lipid-independent catalytic activity. The c.1774G>C, p.(Gly592Arg) variant in contrast shows a defect in substrate phosphorylation representing a loss-of-function mutation.

c.1774G>C, p.(Gly592Arg) is recurrent, reported in 3/5 individuals.; Changed publications: 27479907, 32817298; Changed phenotypes: Congenital heart defects and ectodermal dysplasia, MIM#617364; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.4513 PRKD1 Zornitza Stark Deleted their comment
Fetal anomalies v0.4513 PRKD1 Zornitza Stark Deleted their comment
Fetal anomalies v0.4513 PRSS56 Zornitza Stark Marked gene: PRSS56 as ready
Fetal anomalies v0.4513 PRSS56 Zornitza Stark Gene: prss56 has been classified as Green List (High Evidence).
Fetal anomalies v0.4513 PRSS56 Zornitza Stark Phenotypes for gene: PRSS56 were changed from MICROPHTHALMIA ISOLATED TYPE 6 to Microphthalmia, isolated 6, MIM# 613517
Fetal anomalies v0.4512 PRSS56 Zornitza Stark Publications for gene: PRSS56 were set to
Fetal anomalies v0.4511 RAB18 Zornitza Stark Marked gene: RAB18 as ready
Fetal anomalies v0.4511 RAB18 Zornitza Stark Gene: rab18 has been classified as Green List (High Evidence).
Fetal anomalies v0.4511 RAB18 Zornitza Stark Phenotypes for gene: RAB18 were changed from WARBURG MICRO SYNDROME TYPE 3 to Warburg micro syndrome 3, MIM# 614222
Fetal anomalies v0.4510 RAB18 Zornitza Stark Publications for gene: RAB18 were set to
Fetal anomalies v0.4509 RAB3GAP1 Zornitza Stark Marked gene: RAB3GAP1 as ready
Fetal anomalies v0.4509 RAB3GAP1 Zornitza Stark Gene: rab3gap1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4509 RAB3GAP1 Zornitza Stark Phenotypes for gene: RAB3GAP1 were changed from WARBURG MICRO SYNDROME TYPE 1 to Warburg micro syndrome 1, MIM# 600118; Martsolf syndrome 2, MIM# 619420
Fetal anomalies v0.4508 RAB3GAP1 Zornitza Stark Publications for gene: RAB3GAP1 were set to
Fetal anomalies v0.4507 RAB3GAP2 Zornitza Stark Marked gene: RAB3GAP2 as ready
Fetal anomalies v0.4507 RAB3GAP2 Zornitza Stark Gene: rab3gap2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4507 RAB3GAP2 Zornitza Stark Phenotypes for gene: RAB3GAP2 were changed from MARTSOLF SYNDROME to Warburg micro syndrome 2, MIM# 614225
Fetal anomalies v0.4506 RAB3GAP2 Zornitza Stark Publications for gene: RAB3GAP2 were set to
Fetal anomalies v0.4505 RAC1 Zornitza Stark Marked gene: RAC1 as ready
Fetal anomalies v0.4505 RAC1 Zornitza Stark Gene: rac1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4505 RAC1 Zornitza Stark Phenotypes for gene: RAC1 were changed from Developmental Disorders with Diverse Phenotypes to Mental retardation, autosomal dominant 48, MIM# 617751
Fetal anomalies v0.4504 RAC1 Zornitza Stark Publications for gene: RAC1 were set to 30712878; 28886345
Fetal anomalies v0.4503 RAC1 Zornitza Stark Mode of pathogenicity for gene: RAC1 was changed from to Other
Fetal anomalies v0.4502 RAC1 Zornitza Stark Mode of inheritance for gene: RAC1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4501 RAD21 Zornitza Stark Marked gene: RAD21 as ready
Fetal anomalies v0.4501 RAD21 Zornitza Stark Gene: rad21 has been classified as Green List (High Evidence).
Fetal anomalies v0.4501 RAD21 Zornitza Stark Phenotypes for gene: RAD21 were changed from COHESINOPATHY to Cornelia de Lange syndrome 4, MIM# 614701; Holoprosencephaly
Fetal anomalies v0.4500 RAD21 Zornitza Stark Publications for gene: RAD21 were set to
Fetal anomalies v0.4499 RAD21 Zornitza Stark Mode of inheritance for gene: RAD21 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4498 RAF1 Zornitza Stark Marked gene: RAF1 as ready
Fetal anomalies v0.4498 RAF1 Zornitza Stark Gene: raf1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4498 RAF1 Zornitza Stark Phenotypes for gene: RAF1 were changed from NOONAN SYNDROME 5 to Noonan syndrome 5, MIM# 611553
Fetal anomalies v0.4497 RAF1 Zornitza Stark Publications for gene: RAF1 were set to
Fetal anomalies v0.4496 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
Fetal anomalies v0.4495 RAF1 Zornitza Stark Mode of inheritance for gene: RAF1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4494 RAI1 Zornitza Stark Marked gene: RAI1 as ready
Fetal anomalies v0.4494 RAI1 Zornitza Stark Gene: rai1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4494 RAI1 Zornitza Stark Phenotypes for gene: RAI1 were changed from SMITH-MAGENIS SYNDROME to Smith-Magenis syndrome (MIM#182290)
Fetal anomalies v0.4493 RAI1 Zornitza Stark Publications for gene: RAI1 were set to
Fetal anomalies v0.4492 RAI1 Zornitza Stark Mode of inheritance for gene: RAI1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4491 RAI1 Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association, multiple congenital anomalies.
Fetal anomalies v0.4491 RAPSN Zornitza Stark Marked gene: RAPSN as ready
Fetal anomalies v0.4491 RAPSN Zornitza Stark Gene: rapsn has been classified as Green List (High Evidence).
Fetal anomalies v0.4491 RAPSN Zornitza Stark Phenotypes for gene: RAPSN were changed from FETAL AKINESIA DEFORMATION SEQUENCE; CONGENITAL MYASTHENIC SYNDROME WITH ACETYLCHOLINE RECEPTOR DEFICIENCY to Myasthenic syndrome, congenital, 11, associated with acetylcholine receptor deficiency, MIM#616326; Fetal akinesia deformation sequence 2, MIM# 618388
Fetal anomalies v0.4490 RAPSN Zornitza Stark edited their review of gene: RAPSN: Changed phenotypes: Myasthenic syndrome, congenital, 11, associated with acetylcholine receptor deficiency, MIM#616326, Fetal akinesia deformation sequence 2, MIM# 618388
Fetal anomalies v0.4490 RAPSN Zornitza Stark changed review comment from: ID is not part of the phenotype.; to: Fetal akinesia, contractures.
Fetal anomalies v0.4490 RAPSN Zornitza Stark edited their review of gene: RAPSN: Changed rating: GREEN
Fetal anomalies v0.4490 RARB Zornitza Stark Marked gene: RARB as ready
Fetal anomalies v0.4490 RARB Zornitza Stark Gene: rarb has been classified as Green List (High Evidence).
Fetal anomalies v0.4490 RARB Zornitza Stark Phenotypes for gene: RARB were changed from MICROPHTHALMIA AND DIAPHRAGMATIC HERNIA to Microphthalmia, syndromic 12, MIM# 615524
Fetal anomalies v0.4489 RARB Zornitza Stark Publications for gene: RARB were set to
Fetal anomalies v0.4488 RARS2 Zornitza Stark Marked gene: RARS2 as ready
Fetal anomalies v0.4488 RARS2 Zornitza Stark Gene: rars2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4488 RARS2 Zornitza Stark Phenotypes for gene: RARS2 were changed from PONTOCEREBELLAR HYPOPLASIA TYPE 6 to Pontocerebellar hypoplasia, type 6, MIM# 611523
Fetal anomalies v0.4487 RARS2 Zornitza Stark Publications for gene: RARS2 were set to 26083569
Fetal anomalies v0.4486 RARS2 Zornitza Stark changed review comment from: Progressive microcephaly is part of the phenotype. At least three unrelated families reported.; to: Progressive microcephaly, PCH. At least three unrelated families reported.
Fetal anomalies v0.4486 RASA1 Zornitza Stark Marked gene: RASA1 as ready
Fetal anomalies v0.4486 RASA1 Zornitza Stark Gene: rasa1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4486 RASA1 Zornitza Stark Phenotypes for gene: RASA1 were changed from PARKES WEBER SYNDROME; CAPILLARY MALFORMATION-ARTERIOVENOUS MALFORMATION to Capillary malformation-arteriovenous malformation 1, MIM# 608354
Fetal anomalies v0.4485 RASA1 Zornitza Stark Publications for gene: RASA1 were set to
Fetal anomalies v0.4484 RASA1 Zornitza Stark Mode of inheritance for gene: RASA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4483 RASA1 Zornitza Stark changed review comment from: Single individual reported as part of a cohort.
Sources: Literature; to: AV malformations/fistulas, which can be large.
Sources: Literature
Fetal anomalies v0.4483 RASA1 Zornitza Stark edited their review of gene: RASA1: Changed rating: GREEN; Changed phenotypes: Capillary malformation-arteriovenous malformation 1, MIM# 608354
Fetal anomalies v0.4483 RAX Zornitza Stark Marked gene: RAX as ready
Fetal anomalies v0.4483 RAX Zornitza Stark Gene: rax has been classified as Green List (High Evidence).
Fetal anomalies v0.4483 RAX Zornitza Stark Phenotypes for gene: RAX were changed from MICROPHTHALMIA ISOLATED TYPE 3 to Microphthalmia, isolated 3, MIM# 611038
Fetal anomalies v0.4482 RAX Zornitza Stark Publications for gene: RAX were set to
Fetal anomalies v0.4481 RBM8A Zornitza Stark Marked gene: RBM8A as ready
Fetal anomalies v0.4481 RBM8A Zornitza Stark Gene: rbm8a has been classified as Green List (High Evidence).
Fetal anomalies v0.4481 RBM8A Zornitza Stark Phenotypes for gene: RBM8A were changed from THROMBOCYTOPENIA-ABSENT RADIUS SYNDROME to Thrombocytopaenia-absent radius syndrome, MIM# 274000
Fetal anomalies v0.4480 RBM8A Zornitza Stark Tag SV/CNV tag was added to gene: RBM8A.
Fetal anomalies v0.4480 RBPJ Zornitza Stark Marked gene: RBPJ as ready
Fetal anomalies v0.4480 RBPJ Zornitza Stark Gene: rbpj has been classified as Green List (High Evidence).
Fetal anomalies v0.4480 RBPJ Zornitza Stark Phenotypes for gene: RBPJ were changed from ADAMS OLIVER SYNDROME to Adams-Oliver syndrome 3, MIM#614814
Fetal anomalies v0.4479 RBPJ Zornitza Stark Mode of inheritance for gene: RBPJ was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4478 RBPJ Zornitza Stark changed review comment from: One of the original families described as having no intellectual disability and the other with mild, so I don't think ID is a core feature of the phenotype.; to: Transverse limb defects.
Fetal anomalies v0.4478 RBPJ Zornitza Stark edited their review of gene: RBPJ: Changed rating: GREEN
Fetal anomalies v0.4478 RECQL4 Zornitza Stark Marked gene: RECQL4 as ready
Fetal anomalies v0.4478 RECQL4 Zornitza Stark Gene: recql4 has been classified as Green List (High Evidence).
Fetal anomalies v0.4478 MCM7 Krithika Murali gene: MCM7 was added
gene: MCM7 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MCM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCM7 were set to 33654309; 34059554
Phenotypes for gene: MCM7 were set to Meier-Gorlin syndrome; Microcephaly; Intellectual disability; Lipodystrophy; Adrenal insufficiency
Review for gene: MCM7 was set to AMBER
Added comment: Association with congenital microcephaly. No new publications since last PanelApp review

---

MCM7 is a component of the MCM complex, a DNA helicase which is essential for DNA replication. Other components have been linked to disease with phenotypes including microcephaly and ID. MCM7 is not associated with any phenotype in OMIM or G2P at present. ------ Currently there are 3 unrelated pedigrees in literature with different biallelic MCM7 variants associated with disease (see below). Although there is some functional data in support of variant-level deleteriousness or gene-level pathogenicity, the clinical gestalt is very different between the 3 families.

- PMID: 33654309 (2021) - Two unrelated individuals with different compound het variants in MCM7 but disparate clinical features. One patient had typical Meier-Gorlin syndrome (including growth retardation, microcephaly, congenital lung emphysema, absent breast development, microtia, facial dysmorphism) whereas the second case had a multi-system disorder with neonatal progeroid appearance, lipodystrophy and adrenal insufficiency. While small at birth, the second patient did not demonstrate reduced stature or microcephaly at age 14.5 years. Both individuals had normal neurodevelopment. Functional studies using patient-derived fibroblasts demonstrate that the identified MCM7 variants were deleterious at either transcript or protein levels and through interfering with MCM complex formation, impact efficiency of S phase progression.

- PMID: 34059554 (2021) - Homozygous missense variant identified in three affected individuals from a consanguineous family with severe primary microcephaly, severe ID and behavioural abnormalities. Knockdown of Mcm7 in mouse neuroblastoma cells lead to reduced cell viability and proliferation with increased apoptosis, which were rescued by overexpression of wild-type but not mutant MCM7.
Sources: Literature
Fetal anomalies v0.4478 LMNB2 Krithika Murali gene: LMNB2 was added
gene: LMNB2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: LMNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LMNB2 were set to 33033404
Phenotypes for gene: LMNB2 were set to Microcephaly 27, primary, autosomal dominant - MIM#619180
Review for gene: LMNB2 was set to GREEN
Added comment: Almost all reported individuals had congenital microcephaly.
Sources: Literature
Fetal anomalies v0.4478 LMNB1 Krithika Murali gene: LMNB1 was added
gene: LMNB1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: LMNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LMNB1 were set to 32910914
Phenotypes for gene: LMNB1 were set to Microcephaly 26, primary, autosomal dominant - MIM#619179
Review for gene: LMNB1 was set to GREEN
Added comment: Monoallelic variants associated with profound microcephaly - this was noted antenatally in 5 unrelated individuals (total of 8 individuals from 5 families reported)
Sources: Literature
Fetal anomalies v0.4478 LINGO1 Krithika Murali gene: LINGO1 was added
gene: LINGO1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: LINGO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LINGO1 were set to 28837161; 31668702
Phenotypes for gene: LINGO1 were set to Mental retardation, autosomal recessive 64 - MIM#618103
Review for gene: LINGO1 was set to AMBER
Added comment: 5 individuals reported from 2 families. 4 out of the 5 individuals had microcephaly. ID, developmentatl delay, spasticity, hypertonia, feeding problems also reported features. No antenatal information or birth growth parameters provided, but it is possible that microcephaly was antenatal/congenital in onset based on other phenotypic features reported.
Sources: Literature
Fetal anomalies v0.4478 LAGE3 Krithika Murali gene: LAGE3 was added
gene: LAGE3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: LAGE3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: LAGE3 were set to 31069511; 28805828
Phenotypes for gene: LAGE3 were set to Galloway-Mowat syndrome 2, X-linked - MIM#301006
Review for gene: LAGE3 was set to GREEN
Added comment: Phenotypic features detectable antenatally include microcephaly, IUGR and brain malformations.
Sources: Literature
Fetal anomalies v0.4478 KIF21B Krithika Murali gene: KIF21B was added
gene: KIF21B was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: KIF21B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF21B were set to 32415109
Phenotypes for gene: KIF21B were set to Global developmental delay; Intellectual disability; Abnormality of brain morphology; Microcephaly
Review for gene: KIF21B was set to GREEN
Added comment: Monoallelic variants associated with a neurodevelopmental disorder. Phenotypic features include ID, corpus callosum anomalies and microcephaly. PMID 32415109 report 4 unrelated individuals, 2 had IUGR +/- oligohydramnios.
Sources: Literature
Fetal anomalies v0.4478 PSAP Seb Lunke Marked gene: PSAP as ready
Fetal anomalies v0.4478 PSAP Seb Lunke Gene: psap has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4478 PSAP Seb Lunke Phenotypes for gene: PSAP were changed from ATYPICAL KRABBE DISEASE to Combined SAP deficiency, MIM# 611721; Encephalopathy due to prosaposin deficiency, MONDO:0012719; Krabbe disease, atypical, MIM# 611722, MONDO:0012720; Metachromatic leukodystrophy due to SAP-b deficiency, MIM# 249900, MONDO:0009590; Gaucher disease, atypical, MIM# 610539, MONDO:0012517
Fetal anomalies v0.4477 PSAP Seb Lunke Classified gene: PSAP as Amber List (moderate evidence)
Fetal anomalies v0.4477 PSAP Seb Lunke Added comment: Comment on list classification: Onset in infancy, amber for fetal anomalies
Fetal anomalies v0.4477 PSAP Seb Lunke Gene: psap has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4476 PSAP Seb Lunke reviewed gene: PSAP: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined SAP deficiency, MIM# 611721, Encephalopathy due to prosaposin deficiency, MONDO:0012719, Krabbe disease, atypical, MIM# 611722, MONDO:0012720, Metachromatic leukodystrophy due to SAP-b deficiency, MIM# 249900, MONDO:0009590, Gaucher disease, atypical, MIM# 610539, MONDO:0012517 Edit; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11086 PTCH1 Seb Lunke Marked gene: PTCH1 as ready
Mendeliome v0.11086 PTCH1 Seb Lunke Gene: ptch1 has been classified as Green List (High Evidence).
Mendeliome v0.11086 PTCH1 Seb Lunke Phenotypes for gene: PTCH1 were changed from to Holoprosencephaly 7, MIM# 610828
Mendeliome v0.11085 PTCH1 Seb Lunke Publications for gene: PTCH1 were set to
Mendeliome v0.11084 PTCH1 Seb Lunke Mode of inheritance for gene: PTCH1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4476 PTCH1 Seb Lunke Marked gene: PTCH1 as ready
Fetal anomalies v0.4476 PTCH1 Seb Lunke Gene: ptch1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4476 PTCH1 Seb Lunke Publications for gene: PTCH1 were set to
Fetal anomalies v0.4475 PTCH1 Seb Lunke Phenotypes for gene: PTCH1 were changed from HOLOPROSENCEPHALY-7; BASAL CELL NEVUS SYNDROME to Holoprosencephaly 7, MIM# 610828
Mendeliome v0.11083 PTCH1 Seb Lunke reviewed gene: PTCH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11941477, 17001668, 29575684; Phenotypes: Holoprosencephaly 7, MIM# 610828; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4474 PTCH1 Seb Lunke Mode of inheritance for gene: PTCH1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4473 PTPN11 Seb Lunke Marked gene: PTPN11 as ready
Fetal anomalies v0.4473 PTPN11 Seb Lunke Gene: ptpn11 has been classified as Green List (High Evidence).
Fetal anomalies v0.4473 PTPN11 Seb Lunke Phenotypes for gene: PTPN11 were changed from LEOPARD SYNDROME TYPE 1; NOONAN SYNDROME 1 to LEOPARD syndrome 1, AD, MIM#151100 AD; Noonan syndrome 1, AD, MIM#163950
Fetal anomalies v0.4472 PTPN11 Seb Lunke Publications for gene: PTPN11 were set to 30266093; 28425981
Fetal anomalies v0.4471 PTPN11 Seb Lunke Mode of inheritance for gene: PTPN11 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4470 PUF60 Seb Lunke Marked gene: PUF60 as ready
Fetal anomalies v0.4470 PUF60 Seb Lunke Gene: puf60 has been classified as Green List (High Evidence).
Fetal anomalies v0.4470 PUF60 Seb Lunke Phenotypes for gene: PUF60 were changed from PUF60 syndrome to Verheij syndrome, MIM# 615583
Fetal anomalies v0.4469 PUF60 Seb Lunke Publications for gene: PUF60 were set to
Fetal anomalies v0.4468 PUF60 Seb Lunke Mode of inheritance for gene: PUF60 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11083 RECQL4 Seb Lunke Marked gene: RECQL4 as ready
Mendeliome v0.11083 RECQL4 Seb Lunke Gene: recql4 has been classified as Green List (High Evidence).
Mendeliome v0.11083 RECQL4 Seb Lunke Phenotypes for gene: RECQL4 were changed from to Baller-Gerold syndrome, MIM# 218600; RAPADILINO syndrome, MIM# 266280; Rothmund-Thomson syndrome, type 2,MIM# 268400
Mendeliome v0.11082 RECQL4 Seb Lunke Mode of inheritance for gene: RECQL4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11081 RECQL4 Seb Lunke reviewed gene: RECQL4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Baller-Gerold syndrome, MIM# 218600, RAPADILINO syndrome, MIM# 266280, Rothmund-Thomson syndrome, type 2,MIM# 268400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.4467 RECQL4 Seb Lunke Phenotypes for gene: RECQL4 were changed from RAPADILINO SYNDROME; ROTHMUND-THOMSON SYNDROME; BALLER-GEROLD SYNDROME to Baller-Gerold syndrome, MIM# 218600; RAPADILINO syndrome, MIM# 266280; Rothmund-Thomson syndrome, type 2,MIM#268400
Fetal anomalies v0.4466 RERE Seb Lunke Marked gene: RERE as ready
Fetal anomalies v0.4466 RERE Seb Lunke Gene: rere has been classified as Green List (High Evidence).
Fetal anomalies v0.4466 RERE Seb Lunke Phenotypes for gene: RERE were changed from Phenocopy of Proximal 1p36 Deletions to Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart, MIM# 616975
Fetal anomalies v0.4465 RERE Seb Lunke Publications for gene: RERE were set to
Fetal anomalies v0.4464 RERE Seb Lunke Mode of inheritance for gene: RERE was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4463 RET Zornitza Stark Marked gene: RET as ready
Fetal anomalies v0.4463 RET Zornitza Stark Gene: ret has been classified as Green List (High Evidence).
Fetal anomalies v0.4463 RET Zornitza Stark Phenotypes for gene: RET were changed from RENAL AGENESIS; MULTIPLE ENDOCRINE NEOPLASIA IIB to Central hypoventilation syndrome, congenital, MIM#209880; Multiple endocrine neoplasia IIA, MIM#171400; Multiple endocrine neoplasia IIB, MIM#162300
Fetal anomalies v0.4462 RET Zornitza Stark Mode of inheritance for gene: RET was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4461 SNORD118 Zornitza Stark Marked gene: SNORD118 as ready
Fetal anomalies v0.4461 SNORD118 Zornitza Stark Gene: snord118 has been classified as Green List (High Evidence).
Fetal anomalies v0.4461 SNORD118 Zornitza Stark Phenotypes for gene: SNORD118 were changed from Leukoencephalopathy with cerebral calcification & cysts to Leukoencephalopathy, brain calcifications, and cysts, MIM# 614561
Fetal anomalies v0.4460 SNORD118 Zornitza Stark Publications for gene: SNORD118 were set to
Fetal anomalies v0.4459 SNORD118 Zornitza Stark changed review comment from: Many reported individuals have ID; however overall this is a progressive neurological disorder with variable onset, including in late adulthood.; to: Variable onset, including in infancy with brain abnormalities detectable by imaging.
Fetal anomalies v0.4459 SNORD118 Zornitza Stark edited their review of gene: SNORD118: Changed rating: GREEN
Fetal anomalies v0.4459 RET Zornitza Stark changed review comment from: ID is not part of the phenotype.; to: Megacolon is a feature.
Fetal anomalies v0.4459 RET Zornitza Stark edited their review of gene: RET: Changed rating: GREEN
Fetal anomalies v0.4459 RFX6 Zornitza Stark Marked gene: RFX6 as ready
Fetal anomalies v0.4459 RFX6 Zornitza Stark Gene: rfx6 has been classified as Green List (High Evidence).
Fetal anomalies v0.4459 RFX6 Zornitza Stark Phenotypes for gene: RFX6 were changed from MARTINEZ-FRIAS SYNDROME to Mitchell-Riley syndrome, MIM#615710
Fetal anomalies v0.4458 RFX6 Zornitza Stark Publications for gene: RFX6 were set to
Fetal anomalies v0.4457 RFX6 Zornitza Stark edited their review of gene: RFX6: Changed publications: 20148032, 26264437
Fetal anomalies v0.4457 RFX6 Zornitza Stark changed review comment from: ID is not part of the phenotype.; to: Intestinal atresia.
Fetal anomalies v0.4457 RFX6 Zornitza Stark edited their review of gene: RFX6: Changed rating: GREEN
Fetal anomalies v0.4457 RIPK4 Zornitza Stark Marked gene: RIPK4 as ready
Fetal anomalies v0.4457 RIPK4 Zornitza Stark Gene: ripk4 has been classified as Green List (High Evidence).
Fetal anomalies v0.4457 RIPK4 Zornitza Stark Phenotypes for gene: RIPK4 were changed from POPLITEAL PTERYGIUM SYNDROME, LETHAL TYPE to Popliteal pterygium syndrome, Bartsocas-Papas type, MIM# 263650
Fetal anomalies v0.4456 RIPK4 Zornitza Stark Publications for gene: RIPK4 were set to 28425981
Fetal anomalies v0.4455 RIT1 Zornitza Stark Marked gene: RIT1 as ready
Fetal anomalies v0.4455 RIT1 Zornitza Stark Gene: rit1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4455 RIT1 Zornitza Stark Phenotypes for gene: RIT1 were changed from NOONAN SYNDROME 8 to Noonan syndrome 8, MIM# 615355
Fetal anomalies v0.4454 RIT1 Zornitza Stark Publications for gene: RIT1 were set to 30712878; 28425981
Fetal anomalies v0.4453 RIT1 Zornitza Stark Mode of pathogenicity for gene: RIT1 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Fetal anomalies v0.4453 RIT1 Zornitza Stark Mode of pathogenicity for gene: RIT1 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
Fetal anomalies v0.4452 RIT1 Zornitza Stark Mode of inheritance for gene: RIT1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4451 RMRP Zornitza Stark Marked gene: RMRP as ready
Fetal anomalies v0.4451 RMRP Zornitza Stark Gene: rmrp has been classified as Green List (High Evidence).
Fetal anomalies v0.4451 RMRP Zornitza Stark Phenotypes for gene: RMRP were changed from CARTILAGE-HAIR HYPOPLASIA to Anauxetic dysplasia 1, MIM#607095
Fetal anomalies v0.4450 RMRP Zornitza Stark changed review comment from: Affected individuals are described as having mild ID; note gene is associated with two milder phenotypes, cartilage-hair hypoplasia and metaphyseal dysplasia without hypotrichosis, which are not associated with ID.; to: Skeletal abnormalities; note gene is associated with two milder phenotypes, cartilage-hair hypoplasia and metaphyseal dysplasia without hypotrichosis, which are more subtle.
Fetal anomalies v0.4450 RMRP Zornitza Stark edited their review of gene: RMRP: Changed rating: GREEN
Fetal anomalies v0.4450 RNU4ATAC Zornitza Stark changed review comment from: ID is reported as part of the phenotype. NOTE this gene codes for snRNA, not protein.; to: IUGR. NOTE this gene codes for snRNA, not protein.
Fetal anomalies v0.4450 RNU4ATAC Zornitza Stark Marked gene: RNU4ATAC as ready
Fetal anomalies v0.4450 RNU4ATAC Zornitza Stark Gene: rnu4atac has been classified as Green List (High Evidence).
Fetal anomalies v0.4450 RNU4ATAC Zornitza Stark Phenotypes for gene: RNU4ATAC were changed from MICROCEPHALIC OSTEODYSPLASTIC PRIMORDIAL DWARFISM, TYPE I to Microcephalic osteodysplastic primordial dwarfism, type I, MIM#210710; Roifman syndrome, MIM#616651
Fetal anomalies v0.4449 RNU4ATAC Zornitza Stark Mode of pathogenicity for gene: RNU4ATAC was changed from to Other
Fetal anomalies v0.4448 ROBO1 Zornitza Stark Marked gene: ROBO1 as ready
Fetal anomalies v0.4448 ROBO1 Zornitza Stark Gene: robo1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4448 ROBO1 Zornitza Stark Phenotypes for gene: ROBO1 were changed from Tetralogy of Fallot and septal defects to Tetralogy of Fallot and septal defects; Congenital heart disease, MONDO:0005453
Fetal anomalies v0.4447 ROBO1 Zornitza Stark Phenotypes for gene: ROBO1 were changed from tetralogy of Fallot and septal defects to Tetralogy of Fallot and septal defects
Fetal anomalies v0.4446 ROBO1 Zornitza Stark Mode of inheritance for gene: ROBO1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4445 ROGDI Zornitza Stark Marked gene: ROGDI as ready
Fetal anomalies v0.4445 ROGDI Zornitza Stark Gene: rogdi has been classified as Green List (High Evidence).
Fetal anomalies v0.4445 ROGDI Zornitza Stark Phenotypes for gene: ROGDI were changed from KOHLSCHAYTTER-TANZ SYNDROME to Kohlschutter-Tonz syndrome, MIM# 226750
Fetal anomalies v0.4444 ROGDI Zornitza Stark Publications for gene: ROGDI were set to
Fetal anomalies v0.4443 ROGDI Zornitza Stark changed review comment from: Kohlschutter-Tonz syndrome (KTZS) is an autosomal recessive disorder characterized by severe global developmental delay, early-onset intractable seizures, spasticity, and amelogenesis imperfecta affecting both primary and secondary teeth and causing yellow or brown discolouration of the teeth. More than 10 families reported.; to: Kohlschutter-Tonz syndrome (KTZS) is an autosomal recessive disorder characterized by severe global developmental delay, early-onset intractable seizures, spasticity, and amelogenesis imperfecta affecting both primary and secondary teeth and causing yellow or brown discolouration of the teeth. More than 10 families reported.

Cerebellar hypoplasia and ventriculomegaly described.
Fetal anomalies v0.4443 RPGRIP1L Zornitza Stark Marked gene: RPGRIP1L as ready
Fetal anomalies v0.4443 RPGRIP1L Zornitza Stark Gene: rpgrip1l has been classified as Green List (High Evidence).
Fetal anomalies v0.4443 RPGRIP1L Zornitza Stark Phenotypes for gene: RPGRIP1L were changed from MECKEL SYNDROME TYPE 5; COACH SYNDROME; JOUBERT SYNDROME TYPE 7 to Joubert syndrome 7, MIM# 611560; Meckel syndrome 5, MIM# 611561
Fetal anomalies v0.4442 RPGRIP1L Zornitza Stark Publications for gene: RPGRIP1L were set to
Fetal anomalies v0.4441 RPL11 Zornitza Stark Marked gene: RPL11 as ready
Fetal anomalies v0.4441 RPL11 Zornitza Stark Gene: rpl11 has been classified as Green List (High Evidence).
Fetal anomalies v0.4441 RPL11 Zornitza Stark Phenotypes for gene: RPL11 were changed from Diamond-Blackfan anemia with cleft palate and abnormal thumbs; Diamond-Blackfan anemia 7 612562 to Diamond-Blackfan anemia with cleft palate and abnormal thumbs; Diamond-Blackfan anaemia 7, MIM# 612562; MONDO:0012938
Fetal anomalies v0.4440 RPL11 Zornitza Stark Publications for gene: RPL11 were set to
Fetal anomalies v0.4439 RPL11 Zornitza Stark Mode of inheritance for gene: RPL11 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4438 RPL5 Zornitza Stark Marked gene: RPL5 as ready
Fetal anomalies v0.4438 RPL5 Zornitza Stark Gene: rpl5 has been classified as Green List (High Evidence).
Fetal anomalies v0.4438 RPL5 Zornitza Stark Phenotypes for gene: RPL5 were changed from Diamond-Blackfan anemia 6 612561 to Diamond-Blackfan anaemia 6, MIM# 612561; MONDO:0012937
Fetal anomalies v0.4437 RPL5 Zornitza Stark Publications for gene: RPL5 were set to
Fetal anomalies v0.4436 RPL5 Zornitza Stark Mode of inheritance for gene: RPL5 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4435 RPS10 Zornitza Stark Marked gene: RPS10 as ready
Fetal anomalies v0.4435 RPS10 Zornitza Stark Gene: rps10 has been classified as Green List (High Evidence).
Fetal anomalies v0.4435 RPS10 Zornitza Stark Phenotypes for gene: RPS10 were changed from Diamond-Blackfan anemia 9 613308 to Diamond-Blackfan anaemia 9, MIM# 613308
Fetal anomalies v0.4434 RPS10 Zornitza Stark Publications for gene: RPS10 were set to
Fetal anomalies v0.4433 RPS17 Zornitza Stark Marked gene: RPS17 as ready
Fetal anomalies v0.4433 RPS17 Zornitza Stark Gene: rps17 has been classified as Green List (High Evidence).
Fetal anomalies v0.4433 RPS17 Zornitza Stark Phenotypes for gene: RPS17 were changed from Diamond-Blackfan anemia 4 612527 to Diamond-Blackfan anaemia 4, MIM# 612527
Fetal anomalies v0.4432 RPS17 Zornitza Stark Publications for gene: RPS17 were set to
Fetal anomalies v0.4431 RPS17 Zornitza Stark Mode of inheritance for gene: RPS17 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4430 RPS19 Zornitza Stark Marked gene: RPS19 as ready
Fetal anomalies v0.4430 RPS19 Zornitza Stark Gene: rps19 has been classified as Green List (High Evidence).
Fetal anomalies v0.4430 RPS19 Zornitza Stark Phenotypes for gene: RPS19 were changed from RPS19-RELATED DIAMOND-BLACKFAN ANEMIA to Diamond-Blackfan anaemia 1, MIM# 105650; MONDO:0007110
Fetal anomalies v0.4429 RPS19 Zornitza Stark Publications for gene: RPS19 were set to
Fetal anomalies v0.4428 RPS19 Zornitza Stark Mode of inheritance for gene: RPS19 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4427 RPS26 Zornitza Stark Marked gene: RPS26 as ready
Fetal anomalies v0.4427 RPS26 Zornitza Stark Gene: rps26 has been classified as Green List (High Evidence).
Fetal anomalies v0.4427 RPS26 Zornitza Stark Phenotypes for gene: RPS26 were changed from Diamond-Blackfan anemia 10 613309 to Diamond-Blackfan anemia 10, MIM# 613309; MONDO:0013217
Fetal anomalies v0.4426 RPS26 Zornitza Stark Publications for gene: RPS26 were set to
Fetal anomalies v0.4425 RPS26 Zornitza Stark Mode of inheritance for gene: RPS26 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4424 RTTN Zornitza Stark Marked gene: RTTN as ready
Fetal anomalies v0.4424 RTTN Zornitza Stark Gene: rttn has been classified as Green List (High Evidence).
Fetal anomalies v0.4424 RTTN Zornitza Stark Phenotypes for gene: RTTN were changed from BILATERAL DIFFUSE POLYMICROGYRIA to Microcephaly, short stature, and polymicrogyria with seizures, MIM# 614833; Microcephalic primordial dwarfism due to RTTN deficiency MONDO:0018764
Fetal anomalies v0.4423 RTTN Zornitza Stark Publications for gene: RTTN were set to
Fetal anomalies v0.4422 RTTN Zornitza Stark changed review comment from: More than 10 unrelated families reported, severe microcephaly, ID.; to: More than 10 unrelated families reported, severe microcephaly, PMG.
Fetal anomalies v0.4422 RYR1 Zornitza Stark Marked gene: RYR1 as ready
Fetal anomalies v0.4422 RYR1 Zornitza Stark Gene: ryr1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4422 RYR1 Zornitza Stark Phenotypes for gene: RYR1 were changed from MINICORE MYOPATHY WITH EXTERNAL OPHTHALMOPLEGIA to Fetal akinesia sequence
Fetal anomalies v0.4421 RYR1 Zornitza Stark Publications for gene: RYR1 were set to
Fetal anomalies v0.4420 SALL1 Zornitza Stark Marked gene: SALL1 as ready
Fetal anomalies v0.4420 SALL1 Zornitza Stark Gene: sall1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4420 SALL1 Zornitza Stark Phenotypes for gene: SALL1 were changed from TOWNES-BROCKS SYNDROME to Townes-Brocks syndrome 1, MIM#107480; MONDO:0054581
Fetal anomalies v0.4419 SALL1 Zornitza Stark Mode of inheritance for gene: SALL1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4418 SALL1 Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association, limb and other congenital anomalies.
Fetal anomalies v0.4418 SALL4 Zornitza Stark Marked gene: SALL4 as ready
Fetal anomalies v0.4418 SALL4 Zornitza Stark Gene: sall4 has been classified as Green List (High Evidence).
Fetal anomalies v0.4418 SALL4 Zornitza Stark Phenotypes for gene: SALL4 were changed from ACRO-RENAL-OCULAR SYNDROME; DUANE-RADIAL RAY SYNDROME to Duane-radial ray syndrome, MIM# 607323; MONDO:0011812; IVIC syndrome, MIM# 147750; MONDO:0007836
Fetal anomalies v0.4417 SALL4 Zornitza Stark Mode of inheritance for gene: SALL4 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4416 SATB2 Zornitza Stark Marked gene: SATB2 as ready
Fetal anomalies v0.4416 SATB2 Zornitza Stark Gene: satb2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4416 SATB2 Zornitza Stark Phenotypes for gene: SATB2 were changed from NONSPECIFIC SEVERE ID; SYNDROMAL PIERRE ROBIN SEQUENCE; CLEFT PALATE ISOLATED to Glass syndrome, MIM# 612313; MONDO:0100147
Fetal anomalies v0.4415 SATB2 Zornitza Stark Publications for gene: SATB2 were set to
Fetal anomalies v0.4414 SATB2 Zornitza Stark Mode of inheritance for gene: SATB2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4413 SBDS Zornitza Stark Marked gene: SBDS as ready
Fetal anomalies v0.4413 SBDS Zornitza Stark Gene: sbds has been classified as Green List (High Evidence).
Fetal anomalies v0.4413 SBDS Zornitza Stark Phenotypes for gene: SBDS were changed from SHWACHMAN-DIAMOND SYNDROME to Shwachman-Diamond syndrome, MIM#260400
Fetal anomalies v0.4412 SBDS Zornitza Stark Publications for gene: SBDS were set to
Fetal anomalies v0.4411 SBDS Zornitza Stark changed review comment from: Some cognitive involvement but ID rare, see reference.; to: Multiple skeletal abnormalities.
Fetal anomalies v0.4411 SBDS Zornitza Stark edited their review of gene: SBDS: Changed rating: GREEN
Fetal anomalies v0.4411 SCARF2 Zornitza Stark Marked gene: SCARF2 as ready
Fetal anomalies v0.4411 SCARF2 Zornitza Stark Gene: scarf2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4411 SCARF2 Zornitza Stark Phenotypes for gene: SCARF2 were changed from VAN DEN ENDE-GUPTA SYNDROME to Van den Ende-Gupta syndrome, MIM# 600920
Fetal anomalies v0.4410 SCARF2 Zornitza Stark Publications for gene: SCARF2 were set to
Fetal anomalies v0.4409 SDCCAG8 Zornitza Stark Marked gene: SDCCAG8 as ready
Fetal anomalies v0.4409 SDCCAG8 Zornitza Stark Gene: sdccag8 has been classified as Green List (High Evidence).
Fetal anomalies v0.4409 SDCCAG8 Zornitza Stark Phenotypes for gene: SDCCAG8 were changed from SENIOR-LOKEN SYNDROME 7 to Bardet-Biedl syndrome 16, MIM# 615993; MONDO:0014444; Senior-Loken syndrome 7, MIM# 613615; MONDO:0013326; Nephronophthisis
Fetal anomalies v0.4408 SDCCAG8 Zornitza Stark Publications for gene: SDCCAG8 were set to
Fetal anomalies v0.4407 SEC23B Zornitza Stark Marked gene: SEC23B as ready
Fetal anomalies v0.4407 SEC23B Zornitza Stark Gene: sec23b has been classified as Green List (High Evidence).
Fetal anomalies v0.4407 SEC23B Zornitza Stark Phenotypes for gene: SEC23B were changed from ANEMIA, DYSERYTHROPOIETIC CONGENITAL, TYPE II to Dyserythropoietic anemia, congenital, type II 224100; COPII component SEC23B (Disorders of multiple glycosylation and other glycosylation pathways, V-ATPase deficiencies)
Fetal anomalies v0.4406 SEC23B Zornitza Stark Classified gene: SEC23B as Green List (high evidence)
Fetal anomalies v0.4406 SEC23B Zornitza Stark Gene: sec23b has been classified as Green List (High Evidence).
Fetal anomalies v0.4405 SEC23B Zornitza Stark changed review comment from: Over 20 families reported. Clinical presentation is typically post-natal.; to: Over 20 families reported. Clinical presentation is typically post-natal. However, at least two families reported with fetal hydrops.
Fetal anomalies v0.4405 SEC23B Zornitza Stark edited their review of gene: SEC23B: Changed rating: GREEN; Changed publications: 20381388; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4405 SEC23B Zornitza Stark Classified gene: SEC23B as Red List (low evidence)
Fetal anomalies v0.4405 SEC23B Zornitza Stark Gene: sec23b has been classified as Red List (Low Evidence).
Fetal anomalies v0.4404 SEC23B Zornitza Stark changed review comment from: Over 20 families reported.; to: Over 20 families reported. Clinical presentation is typically post-natal.
Fetal anomalies v0.4404 SEC23B Zornitza Stark edited their review of gene: SEC23B: Changed rating: RED
Fetal anomalies v0.4404 SEMA3A Zornitza Stark Marked gene: SEMA3A as ready
Fetal anomalies v0.4404 SEMA3A Zornitza Stark Gene: sema3a has been classified as Green List (High Evidence).
Fetal anomalies v0.4404 TBC1D7 Krithika Murali gene: TBC1D7 was added
gene: TBC1D7 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TBC1D7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D7 were set to 23687350; 24515783
Phenotypes for gene: TBC1D7 were set to Macrocephaly/megalencephaly syndrome, autosomal recessive - MIM#248000
Review for gene: TBC1D7 was set to AMBER
Added comment: PMID: 24515783 report 2 siblings with biallelic variants. One noted to be macrosomic at birth and parents reported macrocephaly.

PMID: 23687350 report 2 affected siblings. One was noted to be macrocephalic at birth.
Sources: Literature
Fetal anomalies v0.4404 TAOK1 Krithika Murali gene: TAOK1 was added
gene: TAOK1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TAOK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TAOK1 were set to 35091509; 31230721; 33565190
Phenotypes for gene: TAOK1 were set to Developmental delay with or without intellectual impairment or behavioral abnormalities - MIM#619575
Review for gene: TAOK1 was set to GREEN
Added comment: Heterozygous TAOK1 variants associated with developmental delay

PMID 35091509 - complication of polyhydramnios noted in 2 pregnancies in unrelated families

PMID 33565190:
- 1 patient with ventriculomegaly detected 28 week USS and polyhydramnios with secondary complication of multi-suture craniosynostosis
- 1 infant with low birth weight.
- 1 individual - antenatal history includes polyhydramnios at 5 months gestation

PMID 31230721 - report one individual noted to be macrocephalic at birth with cleft palate
Sources: Literature
Fetal anomalies v0.4404 STT3A Krithika Murali gene: STT3A was added
gene: STT3A was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: STT3A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: STT3A were set to 34653363; 23842455; 30701557; 28424003
Phenotypes for gene: STT3A were set to Congenital disorder of glycosylation, type Iw, autosomal dominant - MIM#619714; Congenital disorder of glycosylation, type Iw, autosomal recessive - MIM#615596
Review for gene: STT3A was set to GREEN
Added comment: Biallelic variants associated with an earlier onset of symptoms. PMID: 23842455 report IUGR in one infant. PMID: 28424003 - report 5 affected individuals from one family, birth growth parameters of 4/5 individuals suggestive of growth restriction/relative microcephaly.
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ID/DD reported in all cases (at least 7 individuals from 3 unrelated families, with 2 different homozygous variants in STT3A)

PMID: 34653363 - 16 patients from 9 families with new AD mode of inheritance (both de novo and inherited). All variants were missense within/around acritical active/catalytic sites. Patients aged 3-55yo, with children noted to be "healthy" until reaching young adulthood
Clinical features include dysmorphic features, macrocephaly (6/16), mild-moderate ID/DD (10/16), short stature (8/16), skeletal abnormalities (10/16), muscle cramps (7/16).
Functional studies verifies AR disease is caused by LOF variants, whereas the AD variants cause DN proven by cotransfection in WT yeast resulting in impaired glycosylation (protein levels unchanged).
Sources: Literature
Fetal anomalies v0.4404 RHEB Krithika Murali gene: RHEB was added
gene: RHEB was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: RHEB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RHEB were set to 29051493; 31337748
Phenotypes for gene: RHEB were set to Intellectual disability; Macrocephaly; Focal cortical dysplasia
Review for gene: RHEB was set to GREEN
Added comment: No new publications since last PanelApp review. Reviewed PMID: 29051493 supplementary information - three individuals with short stature and macrocephaly. Limited antenatal information provided/birth HC parameters, but one of the affected individuals was noted to have a large head circumference from 20 weeks gestation. PMID 31337748: Somatic variant in this gene found in one individual with focal cortical dysplasia.

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3 individuals from two families with heterozygous RHEB variants. Two siblings carried the c.110 C > T (p.Pro37Leu) variant, and a sporadic individual carried the c.202 T>C (p.Ser68Pro) allele. All 3 individuals had short stature (−2 to −3 SD) and early brain overgrowth with pronounced macrocephaly during childhood (+2.5/+3 SD). They had severe to profound ID with hypotonia, as well as autism spectrum disorder. 2 of 3 individuals were reported to have epilepsy. In a zebrafish model, overexpression of RHEB produced megalencephaly, supporting a hyperactivating effect. This is supported in mice where loss of RHEB activity does not cause an overt neurological phenotype
Single individual with somatic variants in this gene and focal cortical dysplasia also reported.
Sources: Literature
Fetal anomalies v0.4404 SEPSECS Zornitza Stark Marked gene: SEPSECS as ready
Fetal anomalies v0.4404 SEPSECS Zornitza Stark Gene: sepsecs has been classified as Green List (High Evidence).
Fetal anomalies v0.4404 SEPSECS Zornitza Stark Phenotypes for gene: SEPSECS were changed from Pontocerebellar hypoplasia type 2D to Pontocerebellar hypoplasia type 2D, MIM#613811
Fetal anomalies v0.4403 SEPSECS Zornitza Stark Publications for gene: SEPSECS were set to 26805434; 26888482; 29464431
Fetal anomalies v0.4402 SEPSECS Zornitza Stark Deleted their comment
Fetal anomalies v0.4402 SETD5 Zornitza Stark Marked gene: SETD5 as ready
Fetal anomalies v0.4402 SETD5 Zornitza Stark Gene: setd5 has been classified as Green List (High Evidence).
Fetal anomalies v0.4402 SETD5 Zornitza Stark Phenotypes for gene: SETD5 were changed from MENTAL RETARDATION, AUTOSOMAL DOMINANT 23 to Intellectual disability, autosomal dominant 23 (MIM # 615761)
Fetal anomalies v0.4401 SETD5 Zornitza Stark Publications for gene: SETD5 were set to
Fetal anomalies v0.4400 SHH Zornitza Stark Marked gene: SHH as ready
Fetal anomalies v0.4400 SHH Zornitza Stark Gene: shh has been classified as Green List (High Evidence).
Fetal anomalies v0.4400 SHH Zornitza Stark Phenotypes for gene: SHH were changed from MICROPHTHALMIA ISOLATED WITH COLOBOMA TYPE 5; TRIPHALANGEAL THUMB-POLYSYNDACTYLY SYNDROME; HOLOPROSENCEPHALY TYPE 3; SOLITARY MEDIAN MAXILLARY CENTRAL INCISOR to 1. Holoprosencephaly 3 (MIM#142945), AD; 2. Microphthalmia with coloboma 5 (MIM#611638), AD; 3. Schizencephaly (MIM#269160); 4. Single median maxillary central incisor (MIM#147250) AD
Fetal anomalies v0.4399 SHH Zornitza Stark Publications for gene: SHH were set to
Fetal anomalies v0.4398 SHH Zornitza Stark Mode of inheritance for gene: SHH was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4397 SHOC2 Zornitza Stark Marked gene: SHOC2 as ready
Fetal anomalies v0.4397 SHOC2 Zornitza Stark Gene: shoc2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4397 SHOC2 Zornitza Stark Phenotypes for gene: SHOC2 were changed from NOONAN-LIKE SYNDROME WITH LOOSE ANAGEN HAIR to Noonan syndrome-like with loose anagen hair 1, MIM# 607721
Fetal anomalies v0.4396 SHOC2 Zornitza Stark Publications for gene: SHOC2 were set to
Fetal anomalies v0.4395 SHOC2 Zornitza Stark Mode of pathogenicity for gene: SHOC2 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
Fetal anomalies v0.4394 SHOC2 Zornitza Stark Mode of inheritance for gene: SHOC2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4393 SHOX Zornitza Stark Marked gene: SHOX as ready
Fetal anomalies v0.4393 SHOX Zornitza Stark Gene: shox has been classified as Green List (High Evidence).
Fetal anomalies v0.4393 SHOX Zornitza Stark Phenotypes for gene: SHOX were changed from LANGER MESOMELIC DYSPLASIA; LERI-WEILL DYSCHONDROSTEOSIS to Leri-Weill dyschondrosteosis, MIM# 127300; Langer mesomelic dysplasia, MIM#249700
Fetal anomalies v0.4392 PPP2R5C Krithika Murali gene: PPP2R5C was added
gene: PPP2R5C was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PPP2R5C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPP2R5C were set to 25972378
Phenotypes for gene: PPP2R5C were set to macrocephaly; overgrowth
Review for gene: PPP2R5C was set to AMBER
Added comment: x1 case only in the literature with relative macrocephaly noted at birth.

PMID: 25972378 - Loveday et al 2015 undertook trio exome sequencing in children with an overgrowth syndrome phenotype with unaffected parents. One individual with a de novo PPP2R5C c.468_470delAAC p.Thr157del variant identified. The proband had moderate ID, was born at 37 weeks gestation weighing 3100g (0.8SD) with a head circumference of 36cm (2.4SD).
Sources: Literature
Fetal anomalies v0.4392 SHOX Zornitza Stark Tag SV/CNV tag was added to gene: SHOX.
Fetal anomalies v0.4392 SIL1 Zornitza Stark Marked gene: SIL1 as ready
Fetal anomalies v0.4392 SIL1 Zornitza Stark Gene: sil1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4392 SIL1 Zornitza Stark Publications for gene: SIL1 were set to
Fetal anomalies v0.4391 SIL1 Zornitza Stark reviewed gene: SIL1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Marinesco-Sjogren syndrome (MIM#248800); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Growth failure v1.39 BAP1 Zornitza Stark Phenotypes for gene: BAP1 were changed from syndromic intellectual disability MONDO:0000508 to Kury-Isidor syndrome , MIM#619762
Intellectual disability syndromic and non-syndromic v0.4510 BAP1 Zornitza Stark Phenotypes for gene: BAP1 were changed from syndromic intellectual disability MONDO:0000508 to Kury-Isidor syndrome , MIM#619762
Genetic Epilepsy v0.1456 BAP1 Zornitza Stark Phenotypes for gene: BAP1 were changed from Kury-Isidor syndrome , MIM#619762 to Kury-Isidor syndrome , MIM#619762
Genetic Epilepsy v0.1455 BAP1 Zornitza Stark Phenotypes for gene: BAP1 were changed from syndromic intellectual disability MONDO:0000508 to Kury-Isidor syndrome , MIM#619762
Genetic Epilepsy v0.1454 BAP1 Zornitza Stark reviewed gene: BAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Kury-Isidor syndrome, MIM# 619762; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11081 F8 Zornitza Stark Phenotypes for gene: F8 were changed from Haemophilia A, MIM# 306700; MONDO:0010602 to Haemophilia A, MIM# 306700; MONDO:0010602; Thrombophilia 13, X-linked, due to factor VIII defect, MIM# 301071
Bleeding and Platelet Disorders v1.4 F8 Zornitza Stark Phenotypes for gene: F8 were changed from Haemophilia A, MIM# 306700; MONDO:0010602 to Haemophilia A, MIM# 306700; MONDO:0010602; Thrombophilia 13, X-linked, due to factor VIII defect, MIM# 301071
Fetal anomalies v0.4391 SF3B2 Zornitza Stark Phenotypes for gene: SF3B2 were changed from Craniofacial microsomia to Craniofacial microsomia, MIM#164210
Clefting disorders v0.176 SF3B2 Zornitza Stark Phenotypes for gene: SF3B2 were changed from Craniofacial microsomia to Craniofacial microsomia, MIM#164210
Mendeliome v0.11080 SF3B2 Zornitza Stark Phenotypes for gene: SF3B2 were changed from Craniofacial microsomia to Craniofacial microsomia, MIM#164210
Mandibulofacial Acrofacial dysostosis v1.1 SF3B2 Zornitza Stark Phenotypes for gene: SF3B2 were changed from Craniofacial microsomia to Craniofacial microsomia, MIM#164210
Fetal anomalies v0.4389 SIX3 Zornitza Stark Marked gene: SIX3 as ready
Fetal anomalies v0.4389 SIX3 Zornitza Stark Gene: six3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4389 SIX3 Zornitza Stark Phenotypes for gene: SIX3 were changed from HOLOPROSENCEPHALY to Holoprosencephaly 2, MIM# 157170; Schizencephaly (MIM#269160)
Fetal anomalies v0.4388 SIX3 Zornitza Stark Publications for gene: SIX3 were set to
Fetal anomalies v0.4387 SIX3 Zornitza Stark Mode of inheritance for gene: SIX3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4386 SLC10A7 Zornitza Stark Marked gene: SLC10A7 as ready
Fetal anomalies v0.4386 SLC10A7 Zornitza Stark Gene: slc10a7 has been classified as Green List (High Evidence).
Fetal anomalies v0.4386 SLC10A7 Zornitza Stark Phenotypes for gene: SLC10A7 were changed from Chondrodysplasia with multiple dislocations and amelogenesis imperfecta to Short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis, MIM# 618363
Fetal anomalies v0.4385 SLC10A7 Zornitza Stark Publications for gene: SLC10A7 were set to 29878199; 30082715
Fetal anomalies v0.4384 SLC12A1 Zornitza Stark Marked gene: SLC12A1 as ready
Fetal anomalies v0.4384 SLC12A1 Zornitza Stark Gene: slc12a1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4384 SLC12A1 Zornitza Stark Phenotypes for gene: SLC12A1 were changed from Bartter syndrome, type 1 601678 to Bartter syndrome, type 1, MIM#601678
Fetal anomalies v0.4383 SLC12A1 Zornitza Stark Deleted their comment
Fetal anomalies v0.4383 SLC12A1 Zornitza Stark changed review comment from: Polyhydramnios.; to: Polyhydramnios is a presenting feature.
Fetal anomalies v0.4383 SLC12A1 Zornitza Stark edited their review of gene: SLC12A1: Added comment: Polyhydramnios.; Changed rating: GREEN
Fetal anomalies v0.4383 SLC13A5 Zornitza Stark Marked gene: SLC13A5 as ready
Fetal anomalies v0.4383 SLC13A5 Zornitza Stark Gene: slc13a5 has been classified as Green List (High Evidence).
Fetal anomalies v0.4383 SLC13A5 Zornitza Stark Phenotypes for gene: SLC13A5 were changed from EPILEPTIC ENCEPHALOPATHY WITH SEIZURE ONSET IN THE FIRST DAYS OF LIFE to Developmental and epileptic encephalopathy 25, with amelogenesis imperfecta MIM#615905; MONDO:0014392
Fetal anomalies v0.4382 SLC13A5 Zornitza Stark Publications for gene: SLC13A5 were set to
Fetal anomalies v0.4381 SLC13A5 Zornitza Stark changed review comment from: At least 7 unrelated families reported.; to: At least 7 unrelated families reported. Microcephaly is a feature.
Fetal anomalies v0.4381 SLC16A2 Zornitza Stark Marked gene: SLC16A2 as ready
Fetal anomalies v0.4381 SLC16A2 Zornitza Stark Gene: slc16a2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4381 SLC16A2 Zornitza Stark Phenotypes for gene: SLC16A2 were changed from MCT8 (SLC16A2)-SPECIFIC THYROID HORMONE CELL TRANSPORTER DEFICIENCY to Allan-Herndon-Dudley syndrome, MIM# 300523
Fetal anomalies v0.4380 SLC16A2 Zornitza Stark Publications for gene: SLC16A2 were set to
Fetal anomalies v0.4379 SLC16A2 Zornitza Stark Classified gene: SLC16A2 as Amber List (moderate evidence)
Fetal anomalies v0.4379 SLC16A2 Zornitza Stark Gene: slc16a2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4378 SLC16A2 Zornitza Stark edited their review of gene: SLC16A2: Added comment: Clinical presentation is typically post-natal, including microcephaly of post-natal onset.; Changed rating: AMBER
Fetal anomalies v0.4378 SLC2A10 Zornitza Stark Marked gene: SLC2A10 as ready
Fetal anomalies v0.4378 SLC2A10 Zornitza Stark Gene: slc2a10 has been classified as Green List (High Evidence).
Fetal anomalies v0.4378 SLC2A10 Zornitza Stark Phenotypes for gene: SLC2A10 were changed from ARTERIAL TORTUOSITY SYNDROME to Arterial tortuosity syndrome, MIM# 208050
Fetal anomalies v0.4377 SLC2A10 Zornitza Stark reviewed gene: SLC2A10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Arterial tortuosity syndrome, MIM# 208050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4377 SLC35A2 Zornitza Stark Marked gene: SLC35A2 as ready
Fetal anomalies v0.4377 SLC35A2 Zornitza Stark Gene: slc35a2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4377 SLC35A2 Zornitza Stark Phenotypes for gene: SLC35A2 were changed from CONGENITAL DISORDER OF GLYCOSYLATION to Congenital disorder of glycosylation, type IIm (MIM #300896)
Fetal anomalies v0.4376 SLC35A2 Zornitza Stark Publications for gene: SLC35A2 were set to
Fetal anomalies v0.4375 SLC35A2 Zornitza Stark reviewed gene: SLC35A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type IIm (MIM #300896); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v0.4375 SLC35C1 Zornitza Stark Marked gene: SLC35C1 as ready
Fetal anomalies v0.4375 SLC35C1 Zornitza Stark Gene: slc35c1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4375 SLC35C1 Zornitza Stark Phenotypes for gene: SLC35C1 were changed from CONGENITAL DISORDER OF GLYCOSYLATION TYPE 2C to Congenital disorder of glycosylation, type IIc, MIM# 266265, MONDO:0009953
Fetal anomalies v0.4374 SLC35C1 Zornitza Stark Publications for gene: SLC35C1 were set to
Fetal anomalies v0.4373 SLC35C1 Zornitza Stark Classified gene: SLC35C1 as Amber List (moderate evidence)
Fetal anomalies v0.4373 SLC35C1 Zornitza Stark Gene: slc35c1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4372 SLC35C1 Zornitza Stark changed review comment from: Congenital disorder of glycosylation type IIc (CDG2C) is an autosomal recessive disorder characterized by moderate to severe DD/ID, mild dysmorphism, and impaired neutrophil motility. More than 5 unrelated families reported, note immune dysfunction is not always present.

Microcephaly is a feature.; to: Congenital disorder of glycosylation type IIc (CDG2C) is an autosomal recessive disorder characterized by moderate to severe DD/ID, mild dysmorphism, and impaired neutrophil motility. More than 5 unrelated families reported, note immune dysfunction is not always present.

Microcephaly is a feature. Variable severity, some present in childhood.
Fetal anomalies v0.4372 SLC35C1 Zornitza Stark changed review comment from: Congenital disorder of glycosylation type IIc (CDG2C) is an autosomal recessive disorder characterized by moderate to severe DD/ID, mild dysmorphism, and impaired neutrophil motility. More than 5 unrelated families reported, note immune dysfunction is not always present.; to: Congenital disorder of glycosylation type IIc (CDG2C) is an autosomal recessive disorder characterized by moderate to severe DD/ID, mild dysmorphism, and impaired neutrophil motility. More than 5 unrelated families reported, note immune dysfunction is not always present.

Microcephaly is a feature.
Fetal anomalies v0.4372 SLC35C1 Zornitza Stark edited their review of gene: SLC35C1: Changed rating: AMBER
Fetal anomalies v0.4372 SLC35D1 Zornitza Stark Marked gene: SLC35D1 as ready
Fetal anomalies v0.4372 SLC35D1 Zornitza Stark Gene: slc35d1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4372 SLC35D1 Zornitza Stark Phenotypes for gene: SLC35D1 were changed from SCHNECKENBECKEN DYSPLASIA to Schneckenbecken dysplasia 269250, MONDO:0010013; O-xylosyl/N-acetylgalactosaminylglycan synthesis deficiencies (Disorders of protein O-glycosylation)
Fetal anomalies v0.4371 SLC35D1 Zornitza Stark Publications for gene: SLC35D1 were set to
Fetal anomalies v0.4370 SLC39A8 Zornitza Stark Marked gene: SLC39A8 as ready
Fetal anomalies v0.4370 SLC39A8 Zornitza Stark Gene: slc39a8 has been classified as Green List (High Evidence).
Fetal anomalies v0.4370 SLC39A8 Zornitza Stark Phenotypes for gene: SLC39A8 were changed from Intellectual Disability with Cerebellar Atrophy to Congenital disorder of glycosylation, type IIn , MIM#16721
Fetal anomalies v0.4369 SLC39A8 Zornitza Stark Publications for gene: SLC39A8 were set to
Fetal anomalies v0.4368 SLC39A8 Zornitza Stark changed review comment from: 6 individuals from Hutterite descent and two other unrelated families reported. ID a consistent feature.; to: 6 individuals from Hutterite descent and two other unrelated families reported. Craniosynostosis; brain abnormalities.
Fetal anomalies v0.4368 SLX4 Zornitza Stark commented on gene: SLX4: Multiple congenital anomalies.
Fetal anomalies v0.4368 SLX4 Zornitza Stark Marked gene: SLX4 as ready
Fetal anomalies v0.4368 SLX4 Zornitza Stark Gene: slx4 has been classified as Green List (High Evidence).
Fetal anomalies v0.4368 SLX4 Zornitza Stark Phenotypes for gene: SLX4 were changed from FANCONI ANEMIA COMPLEMENTATION GROUP P to Fanconi anaemia, complementation group P, MIM# 613951; MONDO:0013499
Fetal anomalies v0.4367 SMARCA2 Zornitza Stark Marked gene: SMARCA2 as ready
Fetal anomalies v0.4367 SMARCA2 Zornitza Stark Gene: smarca2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4367 SMARCA2 Zornitza Stark Phenotypes for gene: SMARCA2 were changed from COFFIN SIRIS; NICOLAIDES-BARAITSER SYNDROME to Nicolaides-Baraitser syndrome, MIM #601358; Blepharophimosis-intellectual disability syndrome
Fetal anomalies v0.4366 SMARCA2 Zornitza Stark Publications for gene: SMARCA2 were set to
Fetal anomalies v0.4365 SMARCA2 Zornitza Stark 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
Fetal anomalies v0.4364 SMARCA2 Zornitza Stark Mode of inheritance for gene: SMARCA2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4363 SMARCA4 Zornitza Stark Marked gene: SMARCA4 as ready
Fetal anomalies v0.4363 SMARCA4 Zornitza Stark Gene: smarca4 has been classified as Green List (High Evidence).
Fetal anomalies v0.4363 SMARCA4 Zornitza Stark Phenotypes for gene: SMARCA4 were changed from COFFIN SIRIS; RHABDOID TUMOR PREDISPOSITION SYNDROME 2 to Coffin-Siris syndrome 4, MIM# 614609
Fetal anomalies v0.4362 SMARCA4 Zornitza Stark Publications for gene: SMARCA4 were set to
Fetal anomalies v0.4361 SMARCA4 Zornitza Stark Mode of inheritance for gene: SMARCA4 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4360 SMARCA4 Zornitza Stark changed review comment from: Single individual reported as part of a CDH cohort.
Sources: Literature; to: IUGR and multiple congenital anomalies.
Sources: Literature
Fetal anomalies v0.4360 SMARCA4 Zornitza Stark edited their review of gene: SMARCA4: Changed rating: GREEN; Changed phenotypes: Coffin-Siris syndrome 4, MIM# 614609
Fetal anomalies v0.4360 SMC1A Zornitza Stark Marked gene: SMC1A as ready
Fetal anomalies v0.4360 SMC1A Zornitza Stark Gene: smc1a has been classified as Green List (High Evidence).
Fetal anomalies v0.4360 SMC1A Zornitza Stark Phenotypes for gene: SMC1A were changed from Developmental and epileptic encephalopathy, 85, with or without midline brain defects, MONDO:0026771; Cornelia de Lange syndrome 2, OMIM:300590; Developmental and epileptic encephalopathy 85, with or without midline brain defects, OMIM:301044; Cornelia de Lange syndrome 2, MONDO:0010370 to Developmental and epileptic encephalopathy, 85, with or without midline brain defects, MONDO:0026771; Cornelia de Lange syndrome 2, OMIM:300590; Developmental and epileptic encephalopathy 85, with or without midline brain defects, OMIM:301044; Cornelia de Lange syndrome 2, MONDO:0010370
Fetal anomalies v0.4359 SMC1A Zornitza Stark changed review comment from: CDH is a feature of CdL, but cannot find a report specifically with SMC1A variant.; to: Multiple congenital anomalies syndrome.
Fetal anomalies v0.4359 SMC1A Zornitza Stark edited their review of gene: SMC1A: Changed rating: GREEN
Fetal anomalies v0.4359 SMC3 Zornitza Stark Marked gene: SMC3 as ready
Fetal anomalies v0.4359 SMC3 Zornitza Stark Gene: smc3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4359 SMC3 Zornitza Stark Phenotypes for gene: SMC3 were changed from CORNELIA DE LANGE SYNDROME TYPE 3 to Cornelia de Lange syndrome 3, MIM# 610759
Fetal anomalies v0.4358 SMC3 Zornitza Stark Mode of inheritance for gene: SMC3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4357 SMC3 Zornitza Stark changed review comment from: CDH is a feature of CdL but cannot find specific reports of SMC3 variants.; to: Multiple congenital anomalies syndrome.
Fetal anomalies v0.4357 SMC3 Zornitza Stark edited their review of gene: SMC3: Changed rating: GREEN
Fetal anomalies v0.4357 SMN1 Zornitza Stark Marked gene: SMN1 as ready
Fetal anomalies v0.4357 SMN1 Zornitza Stark Gene: smn1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4357 SMN1 Zornitza Stark Phenotypes for gene: SMN1 were changed from Spinal muscular atrophy 253400; Spinal muscular atrophy 271150; Spinal muscular atrophy 253550; Spinal muscular atrophy 253300 to Spinal muscular atrophy 253400; Spinal muscular atrophy 271150; Spinal muscular atrophy 253550; Spinal muscular atrophy 253300
Fetal anomalies v0.4356 SMN1 Zornitza Stark Tag SV/CNV tag was added to gene: SMN1.
Fetal anomalies v0.4356 SMO Zornitza Stark Marked gene: SMO as ready
Fetal anomalies v0.4356 SMO Zornitza Stark Gene: smo has been classified as Green List (High Evidence).
Fetal anomalies v0.4356 SMO Zornitza Stark Mode of inheritance for gene: SMO was changed from Other to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.4355 SMO Zornitza Stark Deleted their comment
Fetal anomalies v0.4355 SMO Zornitza Stark edited their review of gene: SMO: Added comment: Bi-allelic loss-of-function variations in SMO reported in seven individuals from five independent families. Wide phenotypic spectrum of developmental anomalies affecting the brain (hypothalamic hamartoma and microcephaly), heart (atrioventricular septal defect), skeleton (postaxial polydactyly, narrow chest, and shortening of long bones), and enteric nervous system (aganglionosis).
Somatic recurrent missense variant, L412F causes Curry-Jones syndrome.; Changed publications: 32413283, 27236920; Changed phenotypes: Microcephaly, congenital heart disease, polydactyly, aganglionosis, Pallister-Hall-like syndrome, MIM# 241800; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.4355 SMO Zornitza Stark Phenotypes for gene: SMO were changed from Curry-Jones Syndrome to Curry-Jones syndrome, somatic mosaic, MIM#601707
Fetal anomalies v0.4354 SMO Zornitza Stark Publications for gene: SMO were set to
Fetal anomalies v0.4353 SMO Zornitza Stark Mode of pathogenicity for gene: SMO 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
Fetal anomalies v0.4352 SMO Zornitza Stark Mode of inheritance for gene: SMO was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Fetal anomalies v0.4351 SMOC1 Zornitza Stark Marked gene: SMOC1 as ready
Fetal anomalies v0.4351 SMOC1 Zornitza Stark Gene: smoc1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4351 SMOC1 Zornitza Stark Phenotypes for gene: SMOC1 were changed from OPHTHALMOACROMELIC SYNDROME to Microphthalmia with limb anomalies, MIM# 206920
Fetal anomalies v0.4350 SMOC1 Zornitza Stark Publications for gene: SMOC1 were set to
Fetal anomalies v0.4349 SMPD1 Zornitza Stark Marked gene: SMPD1 as ready
Fetal anomalies v0.4349 SMPD1 Zornitza Stark Gene: smpd1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4349 SMPD1 Zornitza Stark Phenotypes for gene: SMPD1 were changed from NIEMANN-PICK DISEASE TYPE B; NIEMANN-PICK DISEASE TYPE A to Niemann-Pick disease, type A, MIM# 257200; MONDO:0009756
Fetal anomalies v0.4348 SMPD1 Zornitza Stark Publications for gene: SMPD1 were set to
Fetal anomalies v0.4347 ZNHIT3 Zornitza Stark Marked gene: ZNHIT3 as ready
Fetal anomalies v0.4347 ZNHIT3 Zornitza Stark Gene: znhit3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4347 ZNF668 Zornitza Stark Marked gene: ZNF668 as ready
Fetal anomalies v0.4347 ZNF668 Zornitza Stark Gene: znf668 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4347 ZNF668 Zornitza Stark Publications for gene: ZNF668 were set to PMID: 34313816, 26633546
Fetal anomalies v0.4346 PIDD1 Zornitza Stark Marked gene: PIDD1 as ready
Fetal anomalies v0.4346 PIDD1 Zornitza Stark Gene: pidd1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4346 PIDD1 Zornitza Stark Classified gene: PIDD1 as Amber List (moderate evidence)
Fetal anomalies v0.4346 PIDD1 Zornitza Stark Gene: pidd1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4345 ZNF526 Zornitza Stark Marked gene: ZNF526 as ready
Fetal anomalies v0.4345 ZNF526 Zornitza Stark Gene: znf526 has been classified as Green List (High Evidence).
Fetal anomalies v0.4345 YRDC Zornitza Stark Marked gene: YRDC as ready
Fetal anomalies v0.4345 YRDC Zornitza Stark Gene: yrdc has been classified as Green List (High Evidence).
Fetal anomalies v0.4345 YRDC Zornitza Stark Publications for gene: YRDC were set to PMID: 31481669, 34545459
Fetal anomalies v0.4344 NFIB Zornitza Stark Marked gene: NFIB as ready
Fetal anomalies v0.4344 NFIB Zornitza Stark Gene: nfib has been classified as Green List (High Evidence).
Fetal anomalies v0.4344 NFIB Zornitza Stark Classified gene: NFIB as Green List (high evidence)
Fetal anomalies v0.4344 NFIB Zornitza Stark Gene: nfib has been classified as Green List (High Evidence).
Fetal anomalies v0.4343 YIF1B Zornitza Stark Marked gene: YIF1B as ready
Fetal anomalies v0.4343 YIF1B Zornitza Stark Gene: yif1b has been classified as Green List (High Evidence).
Congenital nystagmus v1.6 AP3D1 Zornitza Stark Publications for gene: AP3D1 were set to 26744459; 9697856
Congenital nystagmus v1.5 AP3D1 Zornitza Stark Classified gene: AP3D1 as Green List (high evidence)
Congenital nystagmus v1.5 AP3D1 Zornitza Stark Gene: ap3d1 has been classified as Green List (High Evidence).
Congenital nystagmus v1.4 AP3D1 Zornitza Stark commented on gene: AP3D1: Now four affected individuals from two unrelated families, with a mouse model that recapitulates the human phenotype.
Congenital nystagmus v1.4 AP3D1 Zornitza Stark edited their review of gene: AP3D1: Changed rating: GREEN; Changed publications: 26744459, 9697856, 30472485
Mendeliome v0.11079 AP3D1 Zornitza Stark Classified gene: AP3D1 as Green List (high evidence)
Mendeliome v0.11079 AP3D1 Zornitza Stark Gene: ap3d1 has been classified as Green List (High Evidence).
Mendeliome v0.11078 AP3D1 Zornitza Stark edited their review of gene: AP3D1: Added comment: Now four affected individuals from two unrelated families, with a mouse model that recapitulates the human phenotype.; Changed rating: GREEN; Changed publications: 26744459, 9697856, 30472485; Changed phenotypes: Hermansky-Pudlak syndrome 10, MIM# 617050, Oculocutaneous albinism, Severe neutropaenia, Recurrent infections, Seizures, Hearing loss, Neurodevelopmental delay
Fetal anomalies v0.4343 YIPF5 Zornitza Stark Marked gene: YIPF5 as ready
Fetal anomalies v0.4343 YIPF5 Zornitza Stark Gene: yipf5 has been classified as Green List (High Evidence).
Fetal anomalies v0.4343 WDR4 Zornitza Stark Marked gene: WDR4 as ready
Fetal anomalies v0.4343 WDR4 Zornitza Stark Gene: wdr4 has been classified as Green List (High Evidence).
Fetal anomalies v0.4343 WDR37 Zornitza Stark Marked gene: WDR37 as ready
Fetal anomalies v0.4343 WDR37 Zornitza Stark Gene: wdr37 has been classified as Green List (High Evidence).
Fetal anomalies v0.4343 VPS51 Zornitza Stark Marked gene: VPS51 as ready
Fetal anomalies v0.4343 VPS51 Zornitza Stark Gene: vps51 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4343 VPS50 Zornitza Stark Marked gene: VPS50 as ready
Fetal anomalies v0.4343 VPS50 Zornitza Stark Gene: vps50 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4343 VPS4A Zornitza Stark Marked gene: VPS4A as ready
Fetal anomalies v0.4343 VPS4A Zornitza Stark Gene: vps4a has been classified as Green List (High Evidence).
Fetal anomalies v0.4343 TUBGCP2 Zornitza Stark Marked gene: TUBGCP2 as ready
Fetal anomalies v0.4343 TUBGCP2 Zornitza Stark Gene: tubgcp2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4343 HEXB Zornitza Stark Marked gene: HEXB as ready
Fetal anomalies v0.4343 HEXB Zornitza Stark Gene: hexb has been classified as Red List (Low Evidence).
Fetal anomalies v0.4343 HEXB Zornitza Stark Classified gene: HEXB as Red List (low evidence)
Fetal anomalies v0.4343 HEXB Zornitza Stark Gene: hexb has been classified as Red List (Low Evidence).
Fetal anomalies v0.4342 GTPBP2 Zornitza Stark Marked gene: GTPBP2 as ready
Fetal anomalies v0.4342 GTPBP2 Zornitza Stark Gene: gtpbp2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4342 GTPBP2 Zornitza Stark Classified gene: GTPBP2 as Green List (high evidence)
Fetal anomalies v0.4342 GTPBP2 Zornitza Stark Gene: gtpbp2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4341 MCF2 Zornitza Stark Marked gene: MCF2 as ready
Fetal anomalies v0.4341 MCF2 Zornitza Stark Gene: mcf2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4341 MCF2 Zornitza Stark Classified gene: MCF2 as Red List (low evidence)
Fetal anomalies v0.4341 MCF2 Zornitza Stark Gene: mcf2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4340 MAN2C1 Zornitza Stark Marked gene: MAN2C1 as ready
Fetal anomalies v0.4340 MAN2C1 Zornitza Stark Gene: man2c1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4340 MAN2C1 Zornitza Stark Classified gene: MAN2C1 as Green List (high evidence)
Fetal anomalies v0.4340 MAN2C1 Zornitza Stark Gene: man2c1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4339 INTS8 Zornitza Stark Marked gene: INTS8 as ready
Fetal anomalies v0.4339 INTS8 Zornitza Stark Gene: ints8 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4339 INTS8 Zornitza Stark Classified gene: INTS8 as Red List (low evidence)
Fetal anomalies v0.4339 INTS8 Zornitza Stark Gene: ints8 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4338 GRM7 Zornitza Stark Marked gene: GRM7 as ready
Fetal anomalies v0.4338 GRM7 Zornitza Stark Gene: grm7 has been classified as Green List (High Evidence).
Fetal anomalies v0.4338 GRM7 Zornitza Stark Classified gene: GRM7 as Green List (high evidence)
Fetal anomalies v0.4338 GRM7 Zornitza Stark Gene: grm7 has been classified as Green List (High Evidence).
Fetal anomalies v0.4337 ERMARD Zornitza Stark Marked gene: ERMARD as ready
Fetal anomalies v0.4337 ERMARD Zornitza Stark Gene: ermard has been classified as Red List (Low Evidence).
Fetal anomalies v0.4337 ERMARD Zornitza Stark Classified gene: ERMARD as Red List (low evidence)
Fetal anomalies v0.4337 ERMARD Zornitza Stark Gene: ermard has been classified as Red List (Low Evidence).
Fetal anomalies v0.4336 GPT2 Zornitza Stark Marked gene: GPT2 as ready
Fetal anomalies v0.4336 GPT2 Zornitza Stark Gene: gpt2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4336 GPT2 Zornitza Stark Classified gene: GPT2 as Red List (low evidence)
Fetal anomalies v0.4336 GPT2 Zornitza Stark Gene: gpt2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4335 GON7 Zornitza Stark Marked gene: GON7 as ready
Fetal anomalies v0.4335 GON7 Zornitza Stark Gene: gon7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4335 GON7 Zornitza Stark Classified gene: GON7 as Amber List (moderate evidence)
Fetal anomalies v0.4335 GON7 Zornitza Stark Gene: gon7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4334 GON7 Zornitza Stark reviewed gene: GON7: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Galloway-Mowat syndrome 9, MIM# 619603; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4334 EOMES Zornitza Stark Marked gene: EOMES as ready
Fetal anomalies v0.4334 EOMES Zornitza Stark Gene: eomes has been classified as Red List (Low Evidence).
Fetal anomalies v0.4334 EOMES Zornitza Stark Classified gene: EOMES as Red List (low evidence)
Fetal anomalies v0.4334 EOMES Zornitza Stark Gene: eomes has been classified as Red List (Low Evidence).
Fetal anomalies v0.4333 GOLGA2 Zornitza Stark edited their review of gene: GOLGA2: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4333 GOLGA2 Zornitza Stark Marked gene: GOLGA2 as ready
Fetal anomalies v0.4333 GOLGA2 Zornitza Stark Gene: golga2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4333 GOLGA2 Zornitza Stark Phenotypes for gene: GOLGA2 were changed from to neuromuscular disease, GOLGA2-related MONDO#0019056
Fetal anomalies v0.4332 GOLGA2 Zornitza Stark Classified gene: GOLGA2 as Amber List (moderate evidence)
Fetal anomalies v0.4332 GOLGA2 Zornitza Stark Gene: golga2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4331 GOLGA2 Zornitza Stark reviewed gene: GOLGA2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: neuromuscular disease, GOLGA2-related MONDO#0019056; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4331 ENO1 Zornitza Stark Marked gene: ENO1 as ready
Fetal anomalies v0.4331 ENO1 Zornitza Stark Gene: eno1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4331 ENO1 Zornitza Stark Classified gene: ENO1 as Red List (low evidence)
Fetal anomalies v0.4331 ENO1 Zornitza Stark Gene: eno1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4330 CEP85L Zornitza Stark Marked gene: CEP85L as ready
Fetal anomalies v0.4330 CEP85L Zornitza Stark Gene: cep85l has been classified as Green List (High Evidence).
Fetal anomalies v0.4330 CEP85L Zornitza Stark Classified gene: CEP85L as Green List (high evidence)
Fetal anomalies v0.4330 CEP85L Zornitza Stark Gene: cep85l has been classified as Green List (High Evidence).
Fetal anomalies v0.4329 CEP85L Zornitza Stark reviewed gene: CEP85L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lissencephaly 10, posterior predominant (MIM618873); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4329 HEXA Zornitza Stark Marked gene: HEXA as ready
Fetal anomalies v0.4329 HEXA Zornitza Stark Gene: hexa has been classified as Red List (Low Evidence).
Fetal anomalies v0.4329 HEXA Zornitza Stark Classified gene: HEXA as Red List (low evidence)
Fetal anomalies v0.4329 HEXA Zornitza Stark Gene: hexa has been classified as Red List (Low Evidence).
Fetal anomalies v0.4328 FOXR1 Zornitza Stark Marked gene: FOXR1 as ready
Fetal anomalies v0.4328 FOXR1 Zornitza Stark Gene: foxr1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4328 FOXR1 Zornitza Stark Classified gene: FOXR1 as Red List (low evidence)
Fetal anomalies v0.4328 FOXR1 Zornitza Stark Gene: foxr1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4327 FOXR1 Zornitza Stark reviewed gene: FOXR1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v0.4327 HERC1 Zornitza Stark Marked gene: HERC1 as ready
Fetal anomalies v0.4327 HERC1 Zornitza Stark Gene: herc1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4327 HERC1 Zornitza Stark Classified gene: HERC1 as Green List (high evidence)
Fetal anomalies v0.4327 HERC1 Zornitza Stark Gene: herc1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4326 FDXR Zornitza Stark Marked gene: FDXR as ready
Fetal anomalies v0.4326 FDXR Zornitza Stark Gene: fdxr has been classified as Red List (Low Evidence).
Fetal anomalies v0.4326 FDXR Zornitza Stark Classified gene: FDXR as Red List (low evidence)
Fetal anomalies v0.4326 FDXR Zornitza Stark Gene: fdxr has been classified as Red List (Low Evidence).
Fetal anomalies v0.4325 CDK5 Zornitza Stark Marked gene: CDK5 as ready
Fetal anomalies v0.4325 CDK5 Zornitza Stark Gene: cdk5 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4325 CDK5 Zornitza Stark Classified gene: CDK5 as Red List (low evidence)
Fetal anomalies v0.4325 CDK5 Zornitza Stark Gene: cdk5 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4324 EXOC7 Zornitza Stark Marked gene: EXOC7 as ready
Fetal anomalies v0.4324 EXOC7 Zornitza Stark Gene: exoc7 has been classified as Green List (High Evidence).
Fetal anomalies v0.4324 EXOC7 Zornitza Stark Publications for gene: EXOC7 were set to
Fetal anomalies v0.4323 EXOC7 Zornitza Stark Classified gene: EXOC7 as Green List (high evidence)
Fetal anomalies v0.4323 EXOC7 Zornitza Stark Gene: exoc7 has been classified as Green List (High Evidence).
Fetal anomalies v0.4322 EXOC7 Zornitza Stark reviewed gene: EXOC7: Rating: GREEN; Mode of pathogenicity: None; Publications: 32103185; Phenotypes: Neurodevelopmental disorder with seizures and brain atrophy MIM#619072; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4322 DYNC1I2 Zornitza Stark Marked gene: DYNC1I2 as ready
Fetal anomalies v0.4322 DYNC1I2 Zornitza Stark Gene: dync1i2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4322 DYNC1I2 Zornitza Stark Classified gene: DYNC1I2 as Green List (high evidence)
Fetal anomalies v0.4322 DYNC1I2 Zornitza Stark Gene: dync1i2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4321 FIBP Zornitza Stark Marked gene: FIBP as ready
Fetal anomalies v0.4321 FIBP Zornitza Stark Gene: fibp has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4321 FIBP Zornitza Stark Classified gene: FIBP as Amber List (moderate evidence)
Fetal anomalies v0.4321 FIBP Zornitza Stark Gene: fibp has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4320 B3GNT2 Zornitza Stark Marked gene: B3GNT2 as ready
Fetal anomalies v0.4320 B3GNT2 Zornitza Stark Gene: b3gnt2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4320 B3GNT2 Zornitza Stark Classified gene: B3GNT2 as Amber List (moderate evidence)
Fetal anomalies v0.4320 B3GNT2 Zornitza Stark Gene: b3gnt2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4319 CTNNA2 Zornitza Stark Marked gene: CTNNA2 as ready
Fetal anomalies v0.4319 CTNNA2 Zornitza Stark Gene: ctnna2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4319 CTNNA2 Zornitza Stark Classified gene: CTNNA2 as Green List (high evidence)
Fetal anomalies v0.4319 CTNNA2 Zornitza Stark Gene: ctnna2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4318 TUBGCP2 Chirag Patel Classified gene: TUBGCP2 as Green List (high evidence)
Fetal anomalies v0.4318 TUBGCP2 Chirag Patel Gene: tubgcp2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4317 DICER1 Zornitza Stark Marked gene: DICER1 as ready
Fetal anomalies v0.4317 DICER1 Zornitza Stark Gene: dicer1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4317 TUBGCP2 Chirag Patel gene: TUBGCP2 was added
gene: TUBGCP2 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: TUBGCP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TUBGCP2 were set to PMID: 31630790
Phenotypes for gene: TUBGCP2 were set to Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures, OMIM # 618737
Review for gene: TUBGCP2 was set to GREEN
Added comment: Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures (PAMDDFS) is an autosomal recessive neurologic disorder characterized by progressive microcephaly associated with abnormal facial features, hypotonia, and variable global developmental delay with impaired intellectual development. Brain imaging shows variable malformation of cortical development on the lissencephaly spectrum, mainly pachygyria and thin corpus callosum.

4 unrelated patients with homozygous or compound heterozygous mutations in the TUBGCP2 gene, found by WES and segregated with the disorder in all families. Functional studies of the variants were not performed, but analysis of patient fibroblasts derived from the patient with a splice site mutation demonstrated the production of several abnormal transcripts that were predicted to result in a loss of function.
Sources: Expert list
Fetal anomalies v0.4316 DICER1 Zornitza Stark Classified gene: DICER1 as Green List (high evidence)
Fetal anomalies v0.4316 DICER1 Zornitza Stark Gene: dicer1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4315 COPB2 Zornitza Stark Marked gene: COPB2 as ready
Fetal anomalies v0.4315 COPB2 Zornitza Stark Gene: copb2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4315 COPB2 Zornitza Stark Classified gene: COPB2 as Red List (low evidence)
Fetal anomalies v0.4315 COPB2 Zornitza Stark Gene: copb2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4314 ARF1 Zornitza Stark Marked gene: ARF1 as ready
Fetal anomalies v0.4314 ARF1 Zornitza Stark Gene: arf1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4314 ARF1 Zornitza Stark Classified gene: ARF1 as Green List (high evidence)
Fetal anomalies v0.4314 ARF1 Zornitza Stark Gene: arf1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4313 ARF1 Zornitza Stark reviewed gene: ARF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Periventricular nodular heterotopia 8 (MIM#618185); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4313 ATXN2L Zornitza Stark Marked gene: ATXN2L as ready
Fetal anomalies v0.4313 ATXN2L Zornitza Stark Gene: atxn2l has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4313 ATXN2L Zornitza Stark Classified gene: ATXN2L as Amber List (moderate evidence)
Fetal anomalies v0.4313 ATXN2L Zornitza Stark Gene: atxn2l has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4312 VPS4A Chirag Patel Classified gene: VPS4A as Green List (high evidence)
Fetal anomalies v0.4312 VPS4A Chirag Patel Gene: vps4a has been classified as Green List (High Evidence).
Fetal anomalies v0.4311 COPB1 Zornitza Stark Marked gene: COPB1 as ready
Fetal anomalies v0.4311 COPB1 Zornitza Stark Gene: copb1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4311 VPS4A Chirag Patel gene: VPS4A was added
gene: VPS4A was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: VPS4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VPS4A were set to PMID: 33186543; 33186545
Phenotypes for gene: VPS4A were set to CIMDAG syndrome MIM# 619273
Review for gene: VPS4A was set to GREEN
Added comment: CIMDAG syndrome is a multisystemic disorder characterized by severely impaired psychomotor development and hematologic abnormalities apparent from early infancy. Affected individuals show poor overall growth with microcephaly, impaired intellectual development, poor or absent speech, poor eye contact, and motor problems, such as inability to walk, hypotonia, and spasticity. Brain imaging typically shows cerebral and cerebellar atrophy, thin corpus callosum, and delayed myelination. The associated hematologic abnormalities are variable, but are mostly consistent with congenital dyserythropoietic anemia. Eight unrelated patients with de novo heterozygous missense mutations in the VPS4A gene.
Sources: Expert list
Fetal anomalies v0.4311 COPB1 Zornitza Stark Classified gene: COPB1 as Red List (low evidence)
Fetal anomalies v0.4311 COPB1 Zornitza Stark Gene: copb1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4310 CHKA Zornitza Stark Marked gene: CHKA as ready
Fetal anomalies v0.4310 CHKA Zornitza Stark Gene: chka has been classified as Red List (Low Evidence).
Fetal anomalies v0.4310 CHKA Zornitza Stark Classified gene: CHKA as Red List (low evidence)
Fetal anomalies v0.4310 CHKA Zornitza Stark Gene: chka has been classified as Red List (Low Evidence).
Fetal anomalies v0.4309 CENPE Zornitza Stark Marked gene: CENPE as ready
Fetal anomalies v0.4309 CENPE Zornitza Stark Gene: cenpe has been classified as Red List (Low Evidence).
Fetal anomalies v0.4309 CENPE Zornitza Stark Classified gene: CENPE as Red List (low evidence)
Fetal anomalies v0.4309 CENPE Zornitza Stark Gene: cenpe has been classified as Red List (Low Evidence).
Fetal anomalies v0.4308 CDK6 Zornitza Stark Marked gene: CDK6 as ready
Fetal anomalies v0.4308 CDK6 Zornitza Stark Gene: cdk6 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4308 CDK6 Zornitza Stark Classified gene: CDK6 as Amber List (moderate evidence)
Fetal anomalies v0.4308 CDK6 Zornitza Stark Gene: cdk6 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4307 CCDC88A Zornitza Stark Marked gene: CCDC88A as ready
Fetal anomalies v0.4307 CCDC88A Zornitza Stark Gene: ccdc88a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4307 CCDC88A Zornitza Stark Classified gene: CCDC88A as Amber List (moderate evidence)
Fetal anomalies v0.4307 CCDC88A Zornitza Stark Gene: ccdc88a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4306 VPS50 Chirag Patel Classified gene: VPS50 as Amber List (moderate evidence)
Fetal anomalies v0.4306 VPS50 Chirag Patel Gene: vps50 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4305 VPS50 Chirag Patel gene: VPS50 was added
gene: VPS50 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: VPS50 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS50 were set to PMID: 34037727
Phenotypes for gene: VPS50 were set to Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis , MIM#619685
Review for gene: VPS50 was set to AMBER
Added comment: Schneeberger et al (2021 - PMID: 34037727) describe the phenotype of 2 unrelated individuals with biallelic VPS50 variants. Common features included transient neonatal cholestasis, failure to thrive, severe DD with failure to achieve milestones (last examination at 2y and 2y2m respectively), postnatal microcephaly, seizures (onset at 6m and 25m) and irritability. There was corpus callosum hypoplasia on brain imaging. Both individuals were homozygous for variants private to each family (no/not known consanguinity applying to each case). The first individual was homozygous for a splicing variant (NM_017667.4:c.1978-1G>T) and had a similarly unaffected sister deceased with no available DNA for testing. The other individual was homozygous for an in-frame deletion (c.1823_1825delCAA / p.(Thr608del)). VPS50 encodes a critical component of the endosome-associated recycling protein (EARP) complex, which functions in recycling endocytic vesicles back to the plasma membrane [OMIM based on Schindler et al]. The complex contains VPS50, VPS51, VPS52, VPS53, the three latter also being components of GARP (Golgi-associated-retrograde protein) complex. GARP contains VPS54 instead of VPS50 and is required for trafficking of proteins to the trans-golgi network. Thus VPS50 (also named syndetin) and VPS54 function in the EARP and GARP complexes, to define directional movement of their endocytic vesicles [OMIM based on Schindler et al]. The VPS50 subunit is required for recycling of the transferrin receptor. As discussed by Schneeberger et al (refs provided in text): - VPS50 has a high expression in mouse and human brain as well as throughout mouse brain development. - Mice deficient for Vps50 have not been reported. vps50 knockdown in zebrafish results in severe developmental defects of the body axis. Knockout mice for other proteins of the EARP/GARP complex (e.g. Vps52, 53 and 54) display embryonic lethality. Studies performed by Schneeberger et al included: - Transcript analysis for the 1st variant demonstrated skipping of ex21 (in patient derived fabriblasts) leading to an in frame deletion of 81 bp (r.1978_2058del) with predicted loss of 27 residues (p.Leu660_Leu686del). - Similar VPS50 mRNA levels but significant reduction of protein levels (~5% and ~8% of controls) were observed in fibroblasts from patients 1 and 2. Additionally, significant reductions in the amounts of VPS52 and VPS53 protein levels were observed despite mRNA levels similar to controls. Overall, this suggested drastic reduction of functional EARP complex levels. - Lysosomes appeared to have similar morphology, cellular distribution and likely unaffected function in patient fibroblasts. - Transferrin receptor recycling was shown to be delayed in patient fibroblasts suggestive of compromise of endocytic-recycling function. As the authors comment, the phenotype of both individuals with biallelic VPS50 variants overlaps with the corresponding phenotype reported in 15 subjects with biallelic VPS53 or VPS51 mutations notably, severe DD/ID, microcephaly and early onset epilepsy, CC anomalies. Overall, for this group, they propose the term "GARP and/or EARP deficiency disorders". There is no VPS50-associated phenotype in OMIM or G2P. SysID includes VPS50 among the ID candidate genes.
Sources: Expert list
Fetal anomalies v0.4304 VPS51 Chirag Patel Classified gene: VPS51 as Amber List (moderate evidence)
Fetal anomalies v0.4304 VPS51 Chirag Patel Gene: vps51 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4303 VPS51 Chirag Patel gene: VPS51 was added
gene: VPS51 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: VPS51 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS51 were set to PMID: 30624672; 31207318
Phenotypes for gene: VPS51 were set to Pontocerebellar hypoplasia, type 13, MIM# 618606
Review for gene: VPS51 was set to AMBER
Added comment: Pontocerebellar hypoplasia type 13 (PCH13) is an autosomal recessive disorder characterized by global developmental delay, impaired intellectual development with absent speech, microcephaly, and progressive atrophy of the cerebellar vermis and brainstem. Additional features, including seizures and visual impairment. Two families reported with bi-allelic variants in this gene.
Sources: Expert list
Fetal anomalies v0.4302 WDR37 Chirag Patel Classified gene: WDR37 as Green List (high evidence)
Fetal anomalies v0.4302 WDR37 Chirag Patel Gene: wdr37 has been classified as Green List (High Evidence).
Fetal anomalies v0.4301 WDR37 Chirag Patel gene: WDR37 was added
gene: WDR37 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: WDR37 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WDR37 were set to PMID: 31327508, 31327510
Phenotypes for gene: WDR37 were set to Neurooculocardiogenitourinary syndrome MIM#618652
Review for gene: WDR37 was set to GREEN
Added comment: Neurooculocardiogenitourinary syndrome (NOCGUS) is a multisystem disorder characterized by poor growth and anomalies of the ocular, craniofacial, neurologic, cardiovascular, genitourinary, skeletal, and gastrointestinal systems. Lethality before 2 years of age has been observed. Nine unrelated patients reported with de novo missense mutations in the WDR37 gene.
Sources: Expert list
Fetal anomalies v0.4300 WDR4 Chirag Patel Classified gene: WDR4 as Green List (high evidence)
Fetal anomalies v0.4300 WDR4 Chirag Patel Gene: wdr4 has been classified as Green List (High Evidence).
Fetal anomalies v0.4299 WDR4 Chirag Patel gene: WDR4 was added
gene: WDR4 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: WDR4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR4 were set to PubMed: 26416026; 28617965
Phenotypes for gene: WDR4 were set to Microcephaly, growth deficiency, seizures, and brain malformations, OMIM # 618346
Review for gene: WDR4 was set to GREEN
Added comment: Microcephaly, growth deficiency, seizures, and brain malformations (MIGSB) is a severe autosomal recessive disorder characterized by intrauterine growth retardation, postnatal growth deficiency with severe microcephaly, and poor or absent psychomotor development. Additional features include optic atrophy, early-onset seizures, dysmorphic facial features, and brain malformations, such as partial agenesis of the corpus callosum and simplified gyration.

Biallelic variants in the WDR4 gene reported in 4 patients from 3 unrelated families. Studies of patient cells in one family and modeling of the corresponding mutation in yeast showed that the mutation caused a significant reduction in m(7)G46 methylation of specific tRNAs species, particularly at higher temperatures. This was associated with a growth defect in yeast, thus offering a potential mechanism for the growth defects observed in patients with the mutation. The findings suggested that abnormal tRNA modification is a major contributor to disease pathogenesis.
Sources: Literature
Fetal anomalies v0.4298 YIPF5 Chirag Patel Classified gene: YIPF5 as Green List (high evidence)
Fetal anomalies v0.4298 YIPF5 Chirag Patel Gene: yipf5 has been classified as Green List (High Evidence).
Fetal anomalies v0.4297 YIPF5 Chirag Patel gene: YIPF5 was added
gene: YIPF5 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: YIPF5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YIPF5 were set to PMID: 33164986
Phenotypes for gene: YIPF5 were set to Microcephaly, epilepsy, and diabetes syndrome 2 , MIM#619278
Review for gene: YIPF5 was set to GREEN
Added comment: 6 patients from 5 consanguineous families who had microcephaly, epilepsy, and diabetes syndrome (MEDS). All had severe microcephaly (standard deviation of -6.2); epilepsy diagnosed at ages ranging from 1 to 7 months; and neonatal/early-onset diabetes. All patients had low birth weight consistent with reduced insulin secretion in utero.
Sources: Expert list
Disorders of immune dysregulation v0.106 AP3D1 Bryony Thompson Publications for gene: AP3D1 were set to 26744459; 9697856
Disorders of immune dysregulation v0.105 AP3D1 Bryony Thompson Classified gene: AP3D1 as Green List (high evidence)
Disorders of immune dysregulation v0.105 AP3D1 Bryony Thompson Gene: ap3d1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4296 YIF1B Chirag Patel Classified gene: YIF1B as Green List (high evidence)
Fetal anomalies v0.4296 YIF1B Chirag Patel Gene: yif1b has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.104 AP3D1 Bryony Thompson reviewed gene: AP3D1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30472485, 9697856, 26744459; Phenotypes: Hermansky-Pudlak syndrome 10, MIM# 617050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4295 YIF1B Chirag Patel gene: YIF1B was added
gene: YIF1B was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: YIF1B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YIF1B were set to PMID: 32006098; 26077767
Phenotypes for gene: YIF1B were set to Kaya-Barakat-Masson syndrome, MIM# 619125
Review for gene: YIF1B was set to GREEN
Added comment: Kaya-Barakat-Masson syndrome (KABAMAS) is a severe autosomal recessive neurodevelopmental disorder characterized by profoundly impaired global development, peripheral spasticity, dystonia, impaired intellectual development with absent speech, poor eye contact, and feeding difficulties, resulting in poor overall growth, sometimes with microcephaly. Additional more variable features include early-onset seizures, ocular anomalies, foot deformities, and nonspecific brain imaging findings, such as thin corpus callosum and cerebral, cerebellar, or pontine atrophy. Some patients may die in infancy or early childhood.

6 individuals (from 5 families) with biallelic YIF1B truncating variants reported. Presenting features: hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID as well as features suggestive of a motor disorder (dystonia/spasticity/dyskinesia). Seizures were reported in 2 unrelated individuals (2/6). MRI abnormalities were observed in some with thin CC being a feature in 3. Affected individuals were found to be homozygous for truncating variants (4/5 families being consanguineous). The following 3 variants were identified (NM_001039672.2) : c.186dupT or p.Ala64fs / c.360_361insACAT or p.Gly121fs / c.598G>T or p.Glu200*. Yif1B KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). Functional/network analysis of genes co-regulated with YIF1B based on available RNAseq data, suggest enrichement in in genes important for nervous system development and function.
Sources: Expert list
Fetal anomalies v0.4294 NFIB Krithika Murali gene: NFIB was added
gene: NFIB was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: NFIB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NFIB were set to 30388402; 33130023; 32902921
Phenotypes for gene: NFIB were set to Macrocephaly, acquired, with impaired intellectual development - MIM#618286
Review for gene: NFIB was set to GREEN
Added comment: NFIB haploinsufficiency associated with syndromic ID. Macrocephaly and corpus callosum anomalies are recurrent phenotypic features. OMIM notes macrocephaly postnatal in onset, but review of published cases shows some instances of relative macrocephaly at birth. Also corpus callosal anomalies - agenesis and dysgenesis, noted on MRI-B in childhood but possibility of detecting this antenatally in future cases. 2 unrelated individuals reported with minor cardiac anomalies also.

---

OMIM notes macrocephaly postnatal in onset. PMID: 30388402 - 18 individuals reported, of whom 11 had deletions of this gene and the rest had SNVs. Relative macrocephaly noted based on growth parameters in 4 individuals (e.g. x1 male with BW 22nd centile and HC 99th centile in an apparently uncomplicated pregnancy) - macrocephaly became more pronounced with age. In addition, 2 individuals had congenital cardiac anomalies (x1 small VSD and x1 narrow pulmonary artery) and 2 individuals had complete agenesis of the corpus callosum.

33130023 - Report one affected individual. Birth weight was 4.13 kg (Z-score 1.50, 93rd percentile), length was 52 cm (Z-score 1.12, 87th percentile) and his head circumference was 37 cm (Z-score 2.00, 98th percentile). MRI-B at 12 months confirmed agenesis of the corpus callosum

32902921 - report one patient with normal antenatal history, no birth HC provided, macrocephaly noted at 7 months. MRI-B showed mild dysgensis of the corpus callosum age 5. 2nd unrelated patient's birth weight 3.43 kg(57th centile,Zscore 0.17), length 52.8 cm (94th centile, Zscore1.54), and OFC 37.5 cm (99th centile,Zscore 2.39). MRI-B age 5 showed dysgenesis of the corpus callosum.
Sources: Literature
Fetal anomalies v0.4294 YRDC Chirag Patel Classified gene: YRDC as Green List (high evidence)
Fetal anomalies v0.4294 YRDC Chirag Patel Gene: yrdc has been classified as Green List (High Evidence).
Fetal anomalies v0.4293 YRDC Chirag Patel gene: YRDC was added
gene: YRDC was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: YRDC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YRDC were set to PMID: 31481669, 34545459
Phenotypes for gene: YRDC were set to Galloway-Mowat syndrome 10, OMIM # 619609
Review for gene: YRDC was set to GREEN
Added comment: Galloway-Mowat syndrome-10 (GAMOS10) is a severe autosomal recessive disorder characterized by onset of symptoms soon after birth. Affected individuals have progressive renal dysfunction with proteinuria associated with diffuse mesangial sclerosis (DMS) on renal biopsy. Other features include global developmental delay, microcephaly, hypothyroidism, arachnodactyly, and dysmorphic facial features. Some patients may have seizures or abnormalities on brain imaging. All reported patients have died in infancy.

4 individuals from 3 unrelated families with typical features of Galloway-Mowat syndrome including proteinuria, microcephaly, developmental delay and brain malformations. Supportive functional data.
Sources: Expert list
Fetal anomalies v0.4292 ZNF526 Chirag Patel Classified gene: ZNF526 as Green List (high evidence)
Fetal anomalies v0.4292 ZNF526 Chirag Patel Gene: znf526 has been classified as Green List (High Evidence).
Fetal anomalies v0.4291 ZNF526 Chirag Patel gene: ZNF526 was added
gene: ZNF526 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: ZNF526 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF526 were set to PMID: 33397746, 21937992, 25558065,
Phenotypes for gene: ZNF526 were set to Intellectual disability; Microcephaly; Cataracts; Epilepsy; Hypertonia; Dystonia
Review for gene: ZNF526 was set to GREEN
Added comment: - PMID: 21937992 (2011) - Two unrelated families (with 4 affected individuals in each) with non-syndromic ID (mild or moderate, respectively) identified harbouring different biallelic missense variants in the ZNF526 gene.

- PMID: 25558065 (2015) - One family with ID, Noonan-like facies, pulmonary stenosis and a homozygous missense variant in this gene. No further details provided.

- PMID: 33397746 (2021) - Five individuals from four unrelated families with homozygous ZNF526 variants. Four harboured truncating variants, and were all affected by profound DD and severe ID, severe pre/postnatal microcephaly (ranging from -4 SD to -8 SD), bilateral progressive cataracts, hypertonic-dystonic movements, epilepsy and brain MRI anomalies. The fifth patient had a homozygous missense variant and a slightly less severe disorder, with postnatal microcephaly (-2 SD), progressive bilateral cataracts, severe ID, and normal brain MRI. Zebrafish model demonstrated brain and eye malformations resembling findings seen in the human holoprosencephaly spectrum
Sources: Expert list
Fetal anomalies v0.4290 PIDD1 Daniel Flanagan gene: PIDD1 was added
gene: PIDD1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: PIDD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIDD1 were set to 28397838; 29302074; 33414379; 34163010
Phenotypes for gene: PIDD1 were set to Global developmental delay; Intellectual disability; Seizures; Autism; Behavioral abnormality; Psychosis; Pachygyria; Lissencephaly; Abnormality of the corpus callosum
Review for gene: PIDD1 was set to AMBER
Added comment: Doesn't appear to have an antenatal onset. Clinical findings in supplementary table for PMID: 34163010 doesn't mention any prenatal findings. For family M278, two affected siblings were "born at term after uneventful pregnancies, neonatal periods and normal development." Mean age of cohort was 13.2 years.

Biallelic PIDD1 pathogenic variants have been reported in 26 individuals (11 families) with DD (all), variable degrees of ID (mild to severe), behavioral (eg. aggression/self-mutilation in several, ADHD) and/or psychiatric abnormalities (ASD, psychosis in 5 belonging to 3 families), well-controlled epilepsy is some (9 subjects from 6 families) and MRI abnormalities notably abnormal gyration pattern (pachygyria with predominant anterior gradient) as well as corpus callosum anomalies (commonly thinning) in several. Dysmorphic features have been reported in almost all, although there has been no specific feature suggested.

The first reports on the phenotype associated with biallelic PIDD1 mutations were made by Harripaul et al (2018 - PMID: 28397838) and Hu et al (2019 - PMID: 29302074) [both studies investigating large cohorts of individuals with ID from consanguineous families].

Sheikh et al (2021 - PMID: 33414379) provided details on the phenotype of 15 individuals from 5 families including those from the previous 2 reports and studied provided evidence on the role of PIDD1 and the effect of variants.

Zaki et al (2021 - PMID: 34163010) reported 11 additional individuals from 6 consanguineous families, summarize the features of all subjects published in the literature and review the neuroradiological features of the disorder.

PIDD1 encodes p53-induced death domain protein 1. The protein is part of the PIDDosome, a multiprotein complex also composed of the bipartite linker protein CRADD (also known as RAIDD) and the proform of caspase-2 and induces apoptosis in response to DNA damage.

There are 5 potential PIDD1 mRNA transcript variants with NM_145886.4 corresponding to the longest. Similar to the protein encoded by CRADD, PIDD1 contains a death domain (DD - aa 774-893). Constitutive post-translational processing gives PIDD1-N, PIDD1-C the latter further processed into PIDD1-CC (by auto-cleavage). Serine residues at pos. 446 and 588 are involved in this autoprocessing generating PIDD1-C (aa 446-910) and PIDD1-CC (aa 774-893). The latter is needed for caspase-2 activation.

Most (if not all) individuals belonged to consanguineous families of different origins and harbored pLoF or missense variants.

Variants reported so far include : c.2587C>T; p.Gln863* / c.1909C>T ; p.Arg637* / c.2443C>T / p.Arg815Trp / c.2275-1G>A which upon trap assay was shown to lead to skipping of ex15 with direct splicing form exon14 to the terminal exon 16 (resulting to p.Arg759Glyfs*1 with exlcusion of the entire DD) / c.2584C>T; p.Arg862Trp / c.1340G>A; p.Trp447* / c.2116_2120del; p.Val706His*, c.1564_1565del; p.Gly602fs*26

Evidence so far provided includes:
- Biallelic CRADD variants cause a NDD disorder and a highly similar gyration pattern.
- Confirmation of splicing effect (eg. for c.2275-1G>A premature stop in position 760) or poor expression (NM_145886.3:c.2587C>T; p.Gln863*). Arg815Trp did not affect autoprocessing or protein stability.
- Abnormal localization pattern, loss of interaction with CRADD and failure to activate caspase-2 (MDM2 cleavage assay) [p.Gln863* and Arg815Trp]
- Available expression data from GTEx (PIDD1 having broad expression in multiple tissues, but higher in brain cerebellum) as well as BrainSpan and PsychEncode studies suggesting high coexpression of PIDD1, CRADD and CASP2 in many regions in the developing human brain.
- Variants in other genes encoding proteins interacting with PIDD1 (MADD, FADD, DNAJ, etc) are associated with NDD.

Pidd-1 ko mice (ex3-15 removal) lack however CNS-related phenotypes. These show decreased anxiety but no motor anomalies. This has also been the case with Cradd-/- mice displaying no significant CNS phenotypes without lamination defects.
Sources: Expert list
Fetal anomalies v0.4290 ZNF668 Chirag Patel Classified gene: ZNF668 as Amber List (moderate evidence)
Fetal anomalies v0.4290 ZNF668 Chirag Patel Gene: znf668 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4289 ZNF668 Chirag Patel gene: ZNF668 was added
gene: ZNF668 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: ZNF668 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF668 were set to PMID: 34313816, 26633546
Phenotypes for gene: ZNF668 were set to DNA damage repair defect; microcephaly; growth deficiency; severe global developmental delay; brain malformation; facial dysmorphism
Review for gene: ZNF668 was set to AMBER
Added comment: 2 consanguineous families reported with different biallelic truncating (not NMD) variants in ZNF668. Phenotypes included microcephaly, growth deficiency, severe global developmental delay, brain malformation, and distinct facial dysmorphism. Immunofluorescence indicated ZNF668 deficiency. An increased DNA damage phenotype was demonstrated in patient fibroblasts.
Sources: Expert list
Fetal anomalies v0.4288 ZNHIT3 Chirag Patel Classified gene: ZNHIT3 as Green List (high evidence)
Fetal anomalies v0.4288 ZNHIT3 Chirag Patel Gene: znhit3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4287 ZNHIT3 Chirag Patel gene: ZNHIT3 was added
gene: ZNHIT3 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: ZNHIT3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNHIT3 were set to PMID: 28335020; 28335020; 31048081
Phenotypes for gene: ZNHIT3 were set to PEHO syndrome, MIM# 260565
Review for gene: ZNHIT3 was set to GREEN
Added comment: PEHO is a severe autosomal recessive neurodevelopmental disorder characterized by extreme cerebellar atrophy due to almost total loss of granule neurons. Affected individuals present in early infancy with hypotonia, profoundly delayed psychomotor development, optic atrophy, progressive atrophy of the cerebellum and brainstem, and dysmyelination. Most patients also develop infantile seizures that are often associated with hypsarrhythmia on EEG, and many have peripheral oedema. More than 20 affected individuals reported of Finnish origin, p.Ser31Leu is a founder variant. One compound het reported and supportive animal model.
Sources: Expert list
Fetal anomalies v0.4286 GON7 Ain Roesley edited their review of gene: GON7: Changed rating: GREEN
Fetal anomalies v0.4286 APC2 Zornitza Stark Marked gene: APC2 as ready
Fetal anomalies v0.4286 APC2 Zornitza Stark Gene: apc2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4286 APC2 Zornitza Stark Classified gene: APC2 as Green List (high evidence)
Fetal anomalies v0.4286 APC2 Zornitza Stark Gene: apc2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4285 APC2 Zornitza Stark reviewed gene: APC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cortical dysplasia, complex, with other brain malformations 10, MIM#618677; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4285 C7orf43 Zornitza Stark Marked gene: C7orf43 as ready
Fetal anomalies v0.4285 C7orf43 Zornitza Stark Gene: c7orf43 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4285 C7orf43 Zornitza Stark Tag new gene name tag was added to gene: C7orf43.
Fetal anomalies v0.4285 C7orf43 Zornitza Stark Classified gene: C7orf43 as Amber List (moderate evidence)
Fetal anomalies v0.4285 C7orf43 Zornitza Stark Gene: c7orf43 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4284 ATRIP Zornitza Stark Marked gene: ATRIP as ready
Fetal anomalies v0.4284 ATRIP Zornitza Stark Gene: atrip has been classified as Red List (Low Evidence).
Fetal anomalies v0.4284 ATRIP Zornitza Stark Classified gene: ATRIP as Red List (low evidence)
Fetal anomalies v0.4284 ATRIP Zornitza Stark Gene: atrip has been classified as Red List (Low Evidence).
Fetal anomalies v0.4283 ATP9A Zornitza Stark Marked gene: ATP9A as ready
Fetal anomalies v0.4283 ATP9A Zornitza Stark Gene: atp9a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4283 ATP9A Zornitza Stark Classified gene: ATP9A as Amber List (moderate evidence)
Fetal anomalies v0.4283 ATP9A Zornitza Stark Gene: atp9a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4282 ARPC4 Zornitza Stark Marked gene: ARPC4 as ready
Fetal anomalies v0.4282 ARPC4 Zornitza Stark Gene: arpc4 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4282 ARPC4 Zornitza Stark Classified gene: ARPC4 as Red List (low evidence)
Fetal anomalies v0.4282 ARPC4 Zornitza Stark Gene: arpc4 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4281 ANKLE2 Zornitza Stark Marked gene: ANKLE2 as ready
Fetal anomalies v0.4281 ANKLE2 Zornitza Stark Gene: ankle2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4281 ANKLE2 Zornitza Stark Classified gene: ANKLE2 as Green List (high evidence)
Fetal anomalies v0.4281 ANKLE2 Zornitza Stark Gene: ankle2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4280 AGMO Zornitza Stark Marked gene: AGMO as ready
Fetal anomalies v0.4280 AGMO Zornitza Stark Gene: agmo has been classified as Red List (Low Evidence).
Fetal anomalies v0.4280 AGMO Zornitza Stark Classified gene: AGMO as Red List (low evidence)
Fetal anomalies v0.4280 AGMO Zornitza Stark Gene: agmo has been classified as Red List (Low Evidence).
Fetal anomalies v0.4279 ADD3 Zornitza Stark Marked gene: ADD3 as ready
Fetal anomalies v0.4279 ADD3 Zornitza Stark Gene: add3 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4279 ADD3 Zornitza Stark Classified gene: ADD3 as Red List (low evidence)
Fetal anomalies v0.4279 ADD3 Zornitza Stark Gene: add3 has been classified as Red List (Low Evidence).
Mendeliome v0.11078 ADD3 Zornitza Stark edited their review of gene: ADD3: Changed rating: GREEN
Fetal anomalies v0.4278 ADARB1 Zornitza Stark Marked gene: ADARB1 as ready
Fetal anomalies v0.4278 ADARB1 Zornitza Stark Gene: adarb1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4278 ADARB1 Zornitza Stark Classified gene: ADARB1 as Amber List (moderate evidence)
Fetal anomalies v0.4278 ADARB1 Zornitza Stark Gene: adarb1 has been classified as Amber List (Moderate Evidence).
Atypical Haemolytic Uraemic Syndrome_MPGN v0.40 TSEN2 Zornitza Stark Marked gene: TSEN2 as ready
Atypical Haemolytic Uraemic Syndrome_MPGN v0.40 TSEN2 Zornitza Stark Gene: tsen2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4277 D2HGDH Zornitza Stark Marked gene: D2HGDH as ready
Fetal anomalies v0.4277 D2HGDH Zornitza Stark Gene: d2hgdh has been classified as Green List (High Evidence).
Fetal anomalies v0.4277 D2HGDH Zornitza Stark Phenotypes for gene: D2HGDH were changed from to D-2-hydroxyglutaric aciduria, MIM# 600721
Fetal anomalies v0.4276 D2HGDH Zornitza Stark Classified gene: D2HGDH as Green List (high evidence)
Fetal anomalies v0.4276 D2HGDH Zornitza Stark Gene: d2hgdh has been classified as Green List (High Evidence).
Fetal anomalies v0.4275 D2HGDH Zornitza Stark reviewed gene: D2HGDH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: D-2-hydroxyglutaric aciduria, MIM# 600721; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4275 HEXB Krithika Murali gene: HEXB was added
gene: HEXB was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: HEXB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HEXB were set to 23046579; 24613245; 33407268; 27697305; 11869411; 33363784
Phenotypes for gene: HEXB were set to Sandhoff disease, infantile, juvenile, and adult forms-MIM#268800
Review for gene: HEXB was set to RED
Added comment: Biallelic variants associated with Sandhoff disease which includes a severe, infantile onset form. Authors of reported cases note normal antenatal and immediate postnatal course with onset of phenotypic features generally from 2 months of age onwards. Note subset with cardiomyopathy and secondary valvular incompetence, not congenital heart defects.
Sources: Literature
Fetal anomalies v0.4273 GTPBP2 Ain Roesley gene: GTPBP2 was added
gene: GTPBP2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: GTPBP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTPBP2 were set to 26675814; 29449720; 30790272
Phenotypes for gene: GTPBP2 were set to Jaberi-Elahi syndrome MIM#617988
Review for gene: GTPBP2 was set to GREEN
gene: GTPBP2 was marked as current diagnostic
Added comment: Nine individuals from six unrelated families

microcephaly noted but measurements at birth not provided.
1x weight 5th percentile and OFC 25-50 percentile

scoliosis consistently reported
Other features include clenched hands, talipes, abnormal brain imaging, pectus excavatum
Sources: Literature
Fetal anomalies v0.4273 MCF2 Daniel Flanagan gene: MCF2 was added
gene: MCF2 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: MCF2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: MCF2 were set to 31846234
Phenotypes for gene: MCF2 were set to Perisylvian polymicrogyria
Review for gene: MCF2 was set to RED
Added comment: Single individual reported, inherited missense variant from unaffected mother, some support from mouse model.
Sources: Expert list
Fetal anomalies v0.4273 MAN2C1 Daniel Flanagan gene: MAN2C1 was added
gene: MAN2C1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: MAN2C1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAN2C1 were set to 35045343
Phenotypes for gene: MAN2C1 were set to MAN2C1-related neurodevelopmental disorder MONDO:0700092
Review for gene: MAN2C1 was set to GREEN
Added comment: Six individuals from four different families, including two fetuses, exhibiting dysmorphic facial features, congenital anomalies such as tongue hamartoma, variable degrees of intellectual disability, and brain anomalies including polymicrogyria, interhemispheric cysts, hypothalamic hamartoma, callosal anomalies, and hypoplasia of brainstem and cerebellar vermis. Variants include PTC and missense.
*3 unrelated individuals presented polymicrogyria
Sources: Expert list
Fetal anomalies v0.4273 B3GNT2 Belinda Chong commented on gene: B3GNT2
Fetal anomalies v0.4273 INTS8 Daniel Flanagan gene: INTS8 was added
gene: INTS8 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: INTS8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTS8 were set to 28542170
Phenotypes for gene: INTS8 were set to Neurodevelopmental disorder with cerebellar hypoplasia and spasticity (MIM#618572)
Review for gene: INTS8 was set to RED
Added comment: Single family with three affected sibs with compound het INTS8 variants, Microcephaly, Cerebellar hypoplasia, Nodular heterotopia. Some functional evidence.
Sources: Expert list
Fetal anomalies v0.4273 GRM7 Ain Roesley gene: GRM7 was added
gene: GRM7 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: GRM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRM7 were set to 32286009; 32248644
Phenotypes for gene: GRM7 were set to Neurodevelopmental disorder with seizures, hypotonia, and brain abnormalities MIM#618922
Review for gene: GRM7 was set to GREEN
gene: GRM7 was marked as current diagnostic
Added comment: progressive/post-natal microcephaly consistently reported

6 families with 11 affecteds
5 of the pregnancies were complicated by polyhydramnios/decreased fetal movements
Sources: Literature
Fetal anomalies v0.4273 ERMARD Daniel Flanagan gene: ERMARD was added
gene: ERMARD was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: ERMARD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ERMARD were set to 27087860; 24056535
Phenotypes for gene: ERMARD were set to Periventricular nodular heterotopia 6 (MIM#615544)
Review for gene: ERMARD was set to RED
Added comment: Single individual described with heterozygous ERMARD missense and periventricular nodular heterotopia, developmental delay and epilepsy.

PMID: 27087860. Fetus was diagnosed by prenatal ultrasound with symmetric bilateral ventriculomegaly. The fetus carried a 0.78-Mb deletion of chromosomal region 6q27 (ERMARD included).
Sources: Expert list
Fetal anomalies v0.4273 GPT2 Ain Roesley gene: GPT2 was added
gene: GPT2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: GPT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPT2 were set to 25758935; 27601654; 28130718; 29226631; 29882329; 31471722
Phenotypes for gene: GPT2 were set to Neurodevelopmental disorder with microcephaly and spastic paraplegia MIM#616281
Review for gene: GPT2 was set to RED
gene: GPT2 was marked as current diagnostic
Added comment: post-natal microcephaly

of note;
1x family where fisting was observed in a 4 yr old
1x adducted thumbs and scoliosis
a handful had reduced white matter volume and/or thin corpus callosum
Sources: Literature
Fetal anomalies v0.4273 GON7 Ain Roesley edited their review of gene: GON7: Changed rating: AMBER
Fetal anomalies v0.4273 GON7 Ain Roesley gene: GON7 was added
gene: GON7 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: GON7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GON7 were set to 31481669
Phenotypes for gene: GON7 were set to Galloway-Mowat syndrome 9, MIM# 619603
Review for gene: GON7 was set to GREEN
gene: GON7 was marked as current diagnostic
Added comment: 11 individuals from 5 families. Four of the families had the same homozygous variant, shared haplotype suggestive of founder effect.

post-natal microcephaly and brain malformations such as cerebellar atrophy, atrophic/thin corpus callosum. Cranial imaging done as young as 6 months.

Maybe detectable antenatally
Sources: Literature
Fetal anomalies v0.4273 EOMES Daniel Flanagan gene: EOMES was added
gene: EOMES was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: EOMES was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EOMES were set to 17353897
Phenotypes for gene: EOMES were set to microcephaly; polymicrogyria; corpus callosum agenesis
Review for gene: EOMES was set to RED
Added comment: Single family with homozygous balanced translocation between chromosomes 3p and 10q affecting EOMES.
Sources: Expert list
Fetal anomalies v0.4273 GOLGA2 Ain Roesley edited their review of gene: GOLGA2: Changed phenotypes: neuromuscular disease, GOLGA2-related MONDO#0019056
Fetal anomalies v0.4273 GOLGA2 Ain Roesley gene: GOLGA2 was added
gene: GOLGA2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: GOLGA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GOLGA2 were set to 34424553; 26742501; 30237576
Review for gene: GOLGA2 was set to GREEN
gene: GOLGA2 was marked as current diagnostic
Added comment: 3x unrelated families

1x noted with a smaller head at birth head circumference 32.5 cm (7th percentile). weight 3.22 kg (37th percentile), length 49.5 cm (53rd percentile)

Nonspecific cerebral volume loss / cortical atrophy with delayed myelination and thin corpus callosum reported in all post-natally. Maybe detectable antenatally
Sources: Literature
Fetal anomalies v0.4273 APC2 Belinda Chong commented on gene: APC2: Youngest affected was 3 months however, 31585108 indicated All affected children were born full term without any complications during pregnancy and delivery.
Fetal anomalies v0.4273 ENO1 Daniel Flanagan gene: ENO1 was added
gene: ENO1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: ENO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ENO1 were set to 32488097
Phenotypes for gene: ENO1 were set to Polymicrogyria; microcephaly
Review for gene: ENO1 was set to RED
Added comment: ENO1 identified as a polymicrogyria candidate gene from the smallest case of 1p36 duplication reported to date, in a 35yo F (onset at 8mo) presenting intellectual disability, microcephaly, epilepsy and perisylvian polymicrogyria. The duplication only encompassed 2 genes, ENO1 and RERE, and gene expression analysis performed using the patient cells revealed reduced expression, mimicking haploinsufficiency. Eno1 inactivation in rats was shown to cause a brain development defect. According to OMIM, ENO1 is deleted in glioblastoma, which is tolerated by the expression of ENO2.
Sources: Expert list
Fetal anomalies v0.4273 CEP85L Daniel Flanagan gene: CEP85L was added
gene: CEP85L was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: CEP85L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CEP85L were set to 32097630
Phenotypes for gene: CEP85L were set to Lissencephaly 10, posterior predominant (MIM618873)
Review for gene: CEP85L was set to RED
Added comment: Thirteen individuals reported with mono allelic variants in this gene, inherited in two of the families. Mouse model had neuronal migration defects. Earliest symptom onset 5 months, most develop seizures after several years.
Sources: Expert list
Fetal anomalies v0.4273 HEXA Krithika Murali gene: HEXA was added
gene: HEXA was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: HEXA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HEXA were set to Tay-Sachs disease - MIM#272800
Review for gene: HEXA was set to RED
Added comment: Associated features not reported prenatally or at birth.
Sources: Literature
Fetal anomalies v0.4273 FOXR1 Ain Roesley gene: FOXR1 was added
gene: FOXR1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: FOXR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXR1 were set to 34723967
Phenotypes for gene: FOXR1 were set to Postnatal microcephaly, progressive brain atrophy and global developmental delay
Review for gene: FOXR1 was set to AMBER
gene: FOXR1 was marked as current diagnostic
Added comment: 1 individual with functional studies done for the specific variant

post-natal microcephaly with progressive brain atrophy from 1 yr onwards
Sources: Literature
Fetal anomalies v0.4273 HERC1 Krithika Murali gene: HERC1 was added
gene: HERC1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: HERC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HERC1 were set to 28323226; 27108999; 26153217; 26138117
Phenotypes for gene: HERC1 were set to Macrocephaly, dysmorphic facies, and psychomotor retardation - MIM#617011
Review for gene: HERC1 was set to GREEN
Added comment: Multiple individuals reported with macrosomia and macrocephaly detected at birth.
Sources: Literature
Fetal anomalies v0.4273 FDXR Ain Roesley gene: FDXR was added
gene: FDXR was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: FDXR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FDXR were set to 30250212; 28965846
Phenotypes for gene: FDXR were set to Auditory neuropathy and optic atrophy, MIM# 617717
Review for gene: FDXR was set to RED
gene: FDXR was marked as current diagnostic
Added comment: Bi-allelic variants in FDXR cause an autosomal recessive neurologic disorder characterised by onset of visual and hearing impairment in the first or second decades. Two individuals described with a more severe phenotype, including one with microcephaly.
Sources: Literature
Fetal anomalies v0.4273 CDK5 Daniel Flanagan gene: CDK5 was added
gene: CDK5 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CDK5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK5 were set to 25560765
Phenotypes for gene: CDK5 were set to Lissencephaly 7 with cerebellar hypoplasia (MIM#616342)
Review for gene: CDK5 was set to RED
Added comment: Single consanguineous family with multiple affected individuals reported, lissencephaly prominent. Head circumference at the low-normal range (5th–25th percentile).
Sources: Literature
Fetal anomalies v0.4273 EXOC7 Ain Roesley edited their review of gene: EXOC7: Changed publications: 32103185; Changed phenotypes: Neurodevelopmental disorder with seizures and brain atrophy MIM#619072
Fetal anomalies v0.4273 EXOC7 Ain Roesley gene: EXOC7 was added
gene: EXOC7 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: EXOC7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EXOC7 were set to Neurodevelopmental disorder with seizures and brain atrophy MIM#619072
Review for gene: EXOC7 was set to GREEN
gene: EXOC7 was marked as current diagnostic
Added comment: 4 families with 8 affected individuals with brain atrophy, seizures, and developmental delay, and in more severe cases microcephaly and infantile death. Four novel homozygous or comp.heterozygous variants found in EXOC7, which segregated with disease in the families.
Sources: Literature
Fetal anomalies v0.4273 DYNC1I2 Ain Roesley gene: DYNC1I2 was added
gene: DYNC1I2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: DYNC1I2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DYNC1I2 were set to 31079899
Phenotypes for gene: DYNC1I2 were set to Neurodevelopmental disorder with microcephaly and structural brain anomalies , MIM#618492
Review for gene: DYNC1I2 was set to GREEN
gene: DYNC1I2 was marked as current diagnostic
Added comment: 5 affecteds from 3 families

1x microcephaly at birth and head ultrasound at 2 months detected absent corpus callosum. Furthermore, abrain MRI revealed the absence of the rostrum and genu ofthe corpus callosum and partial absence of the splenium,as well as absence of the septum pellucidum and megacisterna magna.

1x microcephaly at birth (-2 SD). Brain MRI at 3 months of age re-vealed a hypoplastic corpus callosum, prominent ventri-cles, reduced white matter volume, and simplified gyralpattern
Sources: Literature
Fetal anomalies v0.4273 FIBP Krithika Murali gene: FIBP was added
gene: FIBP was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: FIBP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FIBP were set to 27183861; 26660953
Phenotypes for gene: FIBP were set to Thauvin-Robinet-Faivre syndrome - MIM#617107
Review for gene: FIBP was set to AMBER
Added comment: Thauvin-Robinet-Faivre syndrome is an autosomal recessive disorder characterized by generalized overgrowth, mainly of height, and mildly delayed psychomotor development with mild or severe learning difficulties. More variable features may include congenital heart defects, kidney abnormalities, and skeletal defects. Patients may have an increased risk for Wilms tumor.

2 unrelated families reported.

27183861 - report one family with 3 affected children. Prenatally relevant phenotypic features include:
- congenital heart disease in one child
- preterm delivery and bilateral talipes equinovarus 2nd child
- cystic kidney disease, nephromegaly and polyhydramnios 3rd child

26660953 - report one child with ventricular septal defect, mitral valve prolapse, renal malrotation with left bifid ureter, macrocephaly and macrosomia noted at birth.
Sources: Literature
Fetal anomalies v0.4273 B3GNT2 Daniel Flanagan gene: B3GNT2 was added
gene: B3GNT2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: B3GNT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B3GNT2 were set to 23359570; 23877401
Phenotypes for gene: B3GNT2 were set to Walker-Warburg syndrome
Review for gene: B3GNT2 was set to AMBER
Added comment: Only 2 families reported

PMID: 23877401. Homozygous frameshift in B3GNT1 identified in a proband born with occipital encephalocele, anencephaly, cloudy cornea, proptotic eyes, spastic posture and micropenis.

PMID: 23359570. Family with two homozygous B3GNT1 missense in affected. 4 pregnancies with abnormalities identified by ultrasound, including: hydrocephalus with the lateral ventricles, severe cerebral ventriculomegaly, cystic dysplastic kidney
Sources: Literature
Fetal anomalies v0.4273 CTNNA2 Ain Roesley gene: CTNNA2 was added
gene: CTNNA2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CTNNA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTNNA2 were set to 30013181
Phenotypes for gene: CTNNA2 were set to Cortical dysplasia, complex, with other brain malformations 9, MIM#618174
Review for gene: CTNNA2 was set to GREEN
gene: CTNNA2 was marked as current diagnostic
Added comment: acquired microcephaly. Pachygyria is also a feature, which can be detectable in a prenatal MRI, though none of the reports thus far were diagnosed antenatally

3 families with 7 affecteds
Sources: Literature
Fetal anomalies v0.4273 DICER1 Krithika Murali gene: DICER1 was added
gene: DICER1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: DICER1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DICER1 were set to 27960159; 29343557; 26227654; 33208384; 35114704; 31232238; 24676357
Phenotypes for gene: DICER1 were set to GLOW syndrome, somatic mosaic - MIM#618272; Goiter, multinodular 1, with or without Sertoli-Leydig cell tumors - MIM#138800; Pleuropulmonary blastoma - MIM#601200
Review for gene: DICER1 was set to GREEN
Added comment: Heterozygous pathogenic germline DICER1 variants are associated with pleuropulmonary blastoma, multinodular goiter, embryonal rhabdomyosarcoma and other tumour types, while mosaic somatic missense DICER1 variants in the RNase IIIb domain are linked to GLOW syndrome (global developmental delay, lung cysts, overgrowth, and Wilms’ tumor) syndrome. While the DICER1 syndrome is classically caused by frameshift, nonsense or other mutations that ablate DICER1 function in a true heterozygous state, GLOW-syndrome mutations occur at specific residues within the RNase IIIb domain that only affect the function of this domain.

Both syndromes have been reported to have features that can be detected prenatally.

PMID 33208384 - report a patient with heterozygous germline DICER1 variant. The patient was born at gestational week 39 after a difficult delivery due to macrocephaly. Clinical findings at birth included two blood vessels in the umbilical cord, undescended testis, inguinal hernia, postaxial polydactyly, ear pits and rocker bottom feet.

PMID: 34331184 - report 4 unrelated families with germline DICER1 variants. In family 1 - one child was born with Pierre Robin sequence, shortening of the left arm and leg and bilateral
hip dysplasia. In Family 2 a child had macrosomia and macrocephaly at birth. Family 4 - born at 33 weeks, dysmorphic facies including hypertelorism and macroglossia.

PMID 24676357 - report 2 unrelated children with GLOW syndrome. Patient 1 was noted to have enlarged kidneys on 24 week ultrasound. At birth was found to have renal and pulmonary cysts. Patient 2 - macrocephaly was noted at birth.

DICER1 implicated in ~60% of PPB - reports of PPB detecteed antenatally, although no reports in the context of confirmed DICER1 syndrome.
Sources: Literature
Fetal anomalies v0.4273 COLGALT1 Zornitza Stark Marked gene: COLGALT1 as ready
Fetal anomalies v0.4273 COLGALT1 Zornitza Stark Gene: colgalt1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4273 COLGALT1 Zornitza Stark Phenotypes for gene: COLGALT1 were changed from to Brain small vessel disease 3, MIM# 618360
Fetal anomalies v0.4272 COLGALT1 Zornitza Stark Publications for gene: COLGALT1 were set to
Fetal anomalies v0.4271 COLGALT1 Zornitza Stark edited their review of gene: COLGALT1: Changed publications: 30412317, 33709034, 31759980
Fetal anomalies v0.4271 COLGALT1 Zornitza Stark commented on gene: COLGALT1: 3 unrelated cases 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.
Fetal anomalies v0.4271 COLGALT1 Zornitza Stark Classified gene: COLGALT1 as Green List (high evidence)
Fetal anomalies v0.4271 COLGALT1 Zornitza Stark Gene: colgalt1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4270 COLGALT1 Zornitza Stark reviewed gene: COLGALT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Brain small vessel disease 3, MIM# 618360; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4270 C2orf69 Zornitza Stark Marked gene: C2orf69 as ready
Fetal anomalies v0.4270 C2orf69 Zornitza Stark Gene: c2orf69 has been classified as Green List (High Evidence).
Fetal anomalies v0.4270 C2orf69 Zornitza Stark Phenotypes for gene: C2orf69 were changed from to Combined oxidative phosphorylation deficiency-53 (COXPD53), MIM#619423
Fetal anomalies v0.4269 C2orf69 Zornitza Stark Classified gene: C2orf69 as Green List (high evidence)
Fetal anomalies v0.4269 C2orf69 Zornitza Stark Gene: c2orf69 has been classified as Green List (High Evidence).
Fetal anomalies v0.4268 C2orf69 Zornitza Stark reviewed gene: C2orf69: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined oxidative phosphorylation deficiency-53 (COXPD53), MIM#619423; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4268 ABHD16A Zornitza Stark Marked gene: ABHD16A as ready
Fetal anomalies v0.4268 ABHD16A Zornitza Stark Gene: abhd16a has been classified as Green List (High Evidence).
Fetal anomalies v0.4268 ABHD16A Zornitza Stark Phenotypes for gene: ABHD16A were changed from to Spastic paraplegia 86, autosomal recessive, MIM# 619735
Fetal anomalies v0.4267 ABHD16A Zornitza Stark Classified gene: ABHD16A as Green List (high evidence)
Fetal anomalies v0.4267 ABHD16A Zornitza Stark Gene: abhd16a has been classified as Green List (High Evidence).
Fetal anomalies v0.4266 ABHD16A Zornitza Stark reviewed gene: ABHD16A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 86, autosomal recessive, MIM# 619735; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11078 ZNFX1 Zornitza Stark Publications for gene: ZNFX1 were set to 33872655; 33876776
Syndromic Retinopathy v0.187 PPP2R3C Zornitza Stark Marked gene: PPP2R3C as ready
Syndromic Retinopathy v0.187 PPP2R3C Zornitza Stark Gene: ppp2r3c has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.187 PPP2R3C Zornitza Stark Classified gene: PPP2R3C as Green List (high evidence)
Syndromic Retinopathy v0.187 PPP2R3C Zornitza Stark Gene: ppp2r3c has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.186 PPP2R3C Zornitza Stark gene: PPP2R3C was added
gene: PPP2R3C was added to Syndromic Retinopathy. Sources: Literature
Mode of inheritance for gene: PPP2R3C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPP2R3C were set to 30893644; 34714774; 34750818
Phenotypes for gene: PPP2R3C were set to Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy, OMIM # 618419
Review for gene: PPP2R3C was set to GREEN
Added comment: Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy (GDRM) is characterized by 46,XY complete gonadal dysgenesis in association with extragonadal anomalies, low birth weight, typical facial gestalt, rod and cone dystrophy, sensorineural hearing loss, omphalocele, anal atresia, renal agenesis, skeletal abnormalities, dry and scaly skin, severe myopathy, and neuromotor delay. 11 unrelated families with syndromic complete gonadal dysgenesis. 9 families had 46,XY females with complete gonadal dysgenesis, but 2 families had 46,XX patients with hypergonadotropic hypogonadism, nonvisualized gonads, primary amenorrhea, and absence of secondary sexual characteristics. Variants segregated with disease in each family and were not found in ethnically matched controls or in public variant databases. The heterozygous fathers exhibited morphologic abnormalities of spermatozoa and reduced fertility.
Sources: Literature
Fetal anomalies v0.4266 COPB2 Ain Roesley gene: COPB2 was added
gene: COPB2 was added to Fetal anomalies. 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 29036432; 34450031
Phenotypes for gene: COPB2 were set to Microcephaly 19, primary, autosomal recessive, MIM# 617800
Review for gene: COPB2 was set to RED
gene: COPB2 was marked as current diagnostic
Added comment: IUGR or small at birth (including microcephaly) not noted for any of the probands. Fractures and osteopenia were not detected antenatally.
Sources: Literature
Mendeliome v0.11077 PPP2R3C Zornitza Stark Marked gene: PPP2R3C as ready
Mendeliome v0.11077 PPP2R3C Zornitza Stark Gene: ppp2r3c has been classified as Green List (High Evidence).
Mendeliome v0.11077 PPP2R3C Zornitza Stark Classified gene: PPP2R3C as Green List (high evidence)
Mendeliome v0.11077 PPP2R3C Zornitza Stark Gene: ppp2r3c has been classified as Green List (High Evidence).
Fetal anomalies v0.4266 ARF1 Daniel Flanagan gene: ARF1 was added
gene: ARF1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ARF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARF1 were set to 28868155; 34353862
Phenotypes for gene: ARF1 were set to Periventricular nodular heterotopia 8 (MIM#618185)
Review for gene: ARF1 was set to RED
Added comment: Three unrelated individuals reported with de novo missense in this gene. PMID: 34353862: Additional report of affected parent and child.

1 patient had microcephaly in teens but normal head circumference at first examination.
Sources: Literature
Fetal anomalies v0.4266 ATXN2L Krithika Murali gene: ATXN2L was added
gene: ATXN2L was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ATXN2L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATXN2L were set to 33283965; 33057194
Phenotypes for gene: ATXN2L were set to macrocephaly; intellectual disability
Review for gene: ATXN2L was set to AMBER
Added comment: Combined data from three large exome groups identified several de novo variants, including frameshift and missense, in ATXN2L in patients with developmental delay (Kaplanis et al., 2020). pLI=1.0

33283965 - Single case report of a novel de novo missense variant in a child with macrocephaly and developmental delay. No functional work. Macrocephaly was detected prenatally. This together with breech presentation resulted in elective C-section at 36 weeks.
Sources: Literature
Fetal anomalies v0.4266 COPB1 Ain Roesley gene: COPB1 was added
gene: COPB1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: COPB1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: COPB1 were set to Baralle-Macken syndrome, MIM# 619255; Severe intellectual disability; variable microcephaly; cataracts
Review for gene: COPB1 was set to RED
gene: COPB1 was marked as current diagnostic
Added comment: Two unrelated families, some supportive functional data. Microcephaly is not a consistent feature in the families reported to date.

Cataracts were also post-natal
Sources: Literature
Fetal anomalies v0.4266 CHKA Ain Roesley gene: CHKA was added
gene: CHKA was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CHKA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHKA were set to 35202461
Phenotypes for gene: CHKA were set to neurodevelopmental disorder, CHKA-related MONDO#0700092
Review for gene: CHKA was set to RED
gene: CHKA was marked as current diagnostic
Added comment: post-natal microcephaly and short stature.
Symptoms which were present within the first few months post birth include developmental delay and seizures
Sources: Literature
Fetal anomalies v0.4266 CENPE Ain Roesley gene: CENPE was added
gene: CENPE was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CENPE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CENPE were set to 24748105; 30086807
Phenotypes for gene: CENPE were set to Microcephaly 13, primary, autosomal recessive (MIM#616051)
Review for gene: CENPE was set to RED
gene: CENPE was marked as current diagnostic
Added comment: PMID: 24748105;
- 2 siblings from non-consanguineous family of European descent
- patient A: at birth, OFC of -5SD which progressed to -9SD at 5 years of age
- patient B: no measurement at birth but OFC was -7SD at 3 years of age
- cHet for 2 missense

*no new reports since. A review of AR primary microcephaly in 2018 still states just 1 family (PMID: 30086807)
Sources: Literature
Fetal anomalies v0.4266 CDK6 Ain Roesley changed review comment from: 1x 8-generational family with 10 affecteds

unclear of microcephaly was present at birth or acquired
Sources: Literature; to: 1x 8-generational family with 10 affecteds

unclear if microcephaly was present at birth or acquired
Sources: Literature
Fetal anomalies v0.4266 CDK6 Ain Roesley gene: CDK6 was added
gene: CDK6 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CDK6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK6 were set to 23918663
Phenotypes for gene: CDK6 were set to Microcephaly 12, primary, autosomal recessive, MIM#616080
Review for gene: CDK6 was set to AMBER
gene: CDK6 was marked as current diagnostic
Added comment: 1x 8-generational family with 10 affecteds

unclear of microcephaly was present at birth or acquired
Sources: Literature
Mendeliome v0.11076 PPP2R3C Zornitza Stark gene: PPP2R3C was added
gene: PPP2R3C was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PPP2R3C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPP2R3C were set to 30893644; 34714774; 34750818
Phenotypes for gene: PPP2R3C were set to Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy, OMIM # 618419
Review for gene: PPP2R3C was set to GREEN
Added comment: Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy (GDRM) is characterized by 46,XY complete gonadal dysgenesis in association with extragonadal anomalies, low birth weight, typical facial gestalt, rod and cone dystrophy, sensorineural hearing loss, omphalocele, anal atresia, renal agenesis, skeletal abnormalities, dry and scaly skin, severe myopathy, and neuromotor delay. 11 unrelated families with syndromic complete gonadal dysgenesis. 9 families had 46,XY females with complete gonadal dysgenesis, but 2 families had 46,XX patients with hypergonadotropic hypogonadism, nonvisualized gonads, primary amenorrhea, and absence of secondary sexual characteristics. Variants segregated with disease in each family and were not found in ethnically matched controls or in public variant databases. The heterozygous fathers exhibited morphologic abnormalities of spermatozoa and reduced fertility.
Sources: Literature
Fetal anomalies v0.4266 CCDC88A Ain Roesley gene: CCDC88A was added
gene: CCDC88A was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CCDC88A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC88A were set to 30392057; 26917597
Phenotypes for gene: CCDC88A were set to PEHO syndrome-like (MIM#617507)
Review for gene: CCDC88A was set to AMBER
gene: CCDC88A was marked as current diagnostic
Added comment: PMID: 26917597;
1x family with 3 affecteds microcephaly (birth OFC -3 - -4 SD)

total of 2 consanguineous families with 5 affecteds and functional studies of KO mice
Sources: Literature
Fetal anomalies v0.4266 PPP2R3C Zornitza Stark Marked gene: PPP2R3C as ready
Fetal anomalies v0.4266 PPP2R3C Zornitza Stark Gene: ppp2r3c has been classified as Green List (High Evidence).
Fetal anomalies v0.4266 APC2 Belinda Chong gene: APC2 was added
gene: APC2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: APC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: APC2 were set to 31585108
Phenotypes for gene: APC2 were set to Cortical dysplasia, complex, with other brain malformations 10, MIM#618677
Review for gene: APC2 was set to RED
gene: APC2 was marked as current diagnostic
Added comment: Onset in infancy

12 individuals from 8 unrelated families; intellectual disability, seizures, cortical dysplasia including posterior to anterior predominant pattern of lissencephaly, heterotopias, paucity of white matter, thin corpus callosum.
Sources: Literature
Fetal anomalies v0.4266 PPP2R3C Zornitza Stark Publications for gene: PPP2R3C were set to PMID: 30893644, 34714774, 34750818
Differences of Sex Development v0.242 PPP2R3C Zornitza Stark Marked gene: PPP2R3C as ready
Differences of Sex Development v0.242 PPP2R3C Zornitza Stark Gene: ppp2r3c has been classified as Green List (High Evidence).
Differences of Sex Development v0.242 PPP2R3C Zornitza Stark Publications for gene: PPP2R3C were set to PMID: 30893644, 34714774, 34750818
Fetal anomalies v0.4265 CDX2 Zornitza Stark Phenotypes for gene: CDX2 were changed from Persistent cloaca to Genetic multiple congenital anomalies/dysmorphic syndrome, MONDO:0043005; Congenital abnormalities of anus, renal and urogenital system, vertebrae and/or the limbs
Fetal anomalies v0.4264 C7orf43 Ain Roesley gene: C7orf43 was added
gene: C7orf43 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: C7orf43 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C7orf43 were set to 30715179
Phenotypes for gene: C7orf43 were set to Microcephaly 25, primary, autosomal recessive, MIM# 618351
Penetrance for gene: C7orf43 were set to Complete
Review for gene: C7orf43 was set to AMBER
gene: C7orf43 was marked as current diagnostic
Added comment: HGNC approved name TRAPPC14

Single family reported: three affected siblings with homozygous truncating variant. Supportive zebrafish model.

Occipital-frontal circumferences were below2 SD at birth, with microcephaly progressing later in life
Sources: Literature
Fetal anomalies v0.4264 ATRIP Ain Roesley gene: ATRIP was added
gene: ATRIP was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ATRIP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATRIP were set to 23144622
Phenotypes for gene: ATRIP were set to Seckel Syndrome
Review for gene: ATRIP was set to RED
gene: ATRIP was marked as current diagnostic
Added comment: Red in Mendeliome - only 1 report of post-natal progressive microcephaly
Sources: Literature
Fetal anomalies v0.4264 ATP9A Ain Roesley gene: ATP9A was added
gene: ATP9A was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ATP9A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP9A were set to 34764295; 34379057
Phenotypes for gene: ATP9A were set to neurodevelopmental disorder, ATP9A-related MONDO#0700092
Penetrance for gene: ATP9A were set to Complete
Review for gene: ATP9A was set to AMBER
gene: ATP9A was marked as current diagnostic
Added comment: post-natal microcephaly, 4 unrelated families

1x polyhydramnios noted and born small, weight of 3570g (−0.41 SD), a length of 50cm (−1.37 SD) and an OFC of 34cm (−1.47 SD).
Sources: Literature
Fetal anomalies v0.4264 ARPC4 Ain Roesley gene: ARPC4 was added
gene: ARPC4 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ARPC4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARPC4 were set to 35047857
Phenotypes for gene: ARPC4 were set to neurodevelopmental disorder, ARPC4-related MONDO#0700092
Penetrance for gene: ARPC4 were set to Complete
Review for gene: ARPC4 was set to RED
gene: ARPC4 was marked as current diagnostic
Added comment: post natal microcephaly except for 1 noted as 4% at birth

7 affected individuals from 6 families (gonadal mosaicism was confirmed in the mother of the 2 affected siblings) with a recurrent missense variant (NM_005718.4:c.472C>T; p.R158C).

Core features in affected individuals include microcephaly, mild motor delays, and significant speech impairment
Sources: Literature
Fetal anomalies v0.4264 ANKLE2 Ain Roesley gene: ANKLE2 was added
gene: ANKLE2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ANKLE2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ANKLE2 were set to 25259927; 30214071; 31735666
Phenotypes for gene: ANKLE2 were set to Microcephaly 16, primary, autosomal recessive, MIM# 616681
Review for gene: ANKLE2 was set to GREEN
gene: ANKLE2 was marked as current diagnostic
Added comment: total of 4 unrelated born with microcephaly
Sources: Literature
Fetal anomalies v0.4264 AGMO Ain Roesley gene: AGMO was added
gene: AGMO was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: AGMO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGMO were set to 31555905; 27000257
Phenotypes for gene: AGMO were set to neurodevelopmental disorder, AGMO-related MONDO#0700092
Penetrance for gene: AGMO were set to Complete
Review for gene: AGMO was set to RED
gene: AGMO was marked as current diagnostic
Added comment: syndromic neurodevelopmental disorder with ID, microcephaly and epilesy reported

1x oligo-hydramnios, maternal hypothyroidism, and decreased fetal movement
birth weight was 2892 g (23%) and length was 49.5 cm (50%). Head circumference was not known but noted to be 5–10%

1x uneventful pregnancy
birth weight was 2977 g (55%) and length was 53.3 cm (98%)

1x siblings with post natal microcephaly
Sources: Literature
Fetal anomalies v0.4264 ADD3 Ain Roesley gene: ADD3 was added
gene: ADD3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ADD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADD3 were set to 23836506; 29768408
Phenotypes for gene: ADD3 were set to Cerebral palsy, spastic quadriplegic, 3 MIM#617008
Penetrance for gene: ADD3 were set to Complete
Review for gene: ADD3 was set to RED
gene: ADD3 was marked as current diagnostic
Added comment: post natal borderline microcephaly and cataract
Sources: Literature
Mendeliome v0.11075 CDX2 Zornitza Stark Phenotypes for gene: CDX2 were changed from Persistent cloaca to Genetic multiple congenital anomalies/dysmorphic syndrome, MONDO:0043005; Congenital abnormalities of anus, renal and urogenital system, vertebrae and/or the limbs
Fetal anomalies v0.4264 ADARB1 Ain Roesley gene: ADARB1 was added
gene: ADARB1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ADARB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADARB1 were set to 32220291; 32719099
Phenotypes for gene: ADARB1 were set to Neurodevelopmental disorder with hypotonia, microcephaly, and seizures, MIM#618862
Penetrance for gene: ADARB1 were set to Complete
Review for gene: ADARB1 was set to AMBER
gene: ADARB1 was marked as current diagnostic
Added comment: 6 unrelated families

1 microcephalic at birth (-2.2 SD) + 1 birth length at -4.3 SD
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4509 CHKA Zornitza Stark Marked gene: CHKA as ready
Intellectual disability syndromic and non-syndromic v0.4509 CHKA Zornitza Stark Gene: chka has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4509 CHKA Zornitza Stark Phenotypes for gene: CHKA were changed from Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature to Neurodevelopmental disorder, MONDO:0700092; Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature
Intellectual disability syndromic and non-syndromic v0.4508 CHKA Zornitza Stark Classified gene: CHKA as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4508 CHKA Zornitza Stark Gene: chka has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1454 CHKA Zornitza Stark Marked gene: CHKA as ready
Genetic Epilepsy v0.1454 CHKA Zornitza Stark Gene: chka has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1454 CHKA Zornitza Stark Phenotypes for gene: CHKA were changed from Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature to Neurodevelopmental disorder, MONDO:0700092; Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature
Genetic Epilepsy v0.1453 CHKA Zornitza Stark Classified gene: CHKA as Green List (high evidence)
Genetic Epilepsy v0.1453 CHKA Zornitza Stark Gene: chka has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1452 CHKA Zornitza Stark Classified gene: CHKA as Green List (high evidence)
Genetic Epilepsy v0.1452 CHKA Zornitza Stark Gene: chka has been classified as Green List (High Evidence).
Microcephaly v1.109 CHKA Zornitza Stark Phenotypes for gene: CHKA were changed from Neurodevelopmental disorder, MONDO:0700092; Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature to Neurodevelopmental disorder, MONDO:0700092; Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature
Microcephaly v1.109 CHKA Zornitza Stark Marked gene: CHKA as ready
Microcephaly v1.109 CHKA Zornitza Stark Gene: chka has been classified as Green List (High Evidence).
Microcephaly v1.109 CHKA Zornitza Stark Phenotypes for gene: CHKA were changed from Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature to Neurodevelopmental disorder, MONDO:0700092; Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature
Microcephaly v1.108 CHKA Zornitza Stark Classified gene: CHKA as Green List (high evidence)
Microcephaly v1.108 CHKA Zornitza Stark Gene: chka has been classified as Green List (High Evidence).
Mendeliome v0.11074 CHKA Zornitza Stark Marked gene: CHKA as ready
Mendeliome v0.11074 CHKA Zornitza Stark Gene: chka has been classified as Green List (High Evidence).
Mendeliome v0.11074 CHKA Zornitza Stark Phenotypes for gene: CHKA were changed from Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature to Neurodevelopmental disorder, MONDO:0700092; Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature
Mendeliome v0.11073 CHKA Zornitza Stark Classified gene: CHKA as Green List (high evidence)
Mendeliome v0.11073 CHKA Zornitza Stark Gene: chka has been classified as Green List (High Evidence).
Fetal anomalies v0.4264 UNC13A Zornitza Stark Marked gene: UNC13A as ready
Fetal anomalies v0.4264 UNC13A Zornitza Stark Gene: unc13a has been classified as Red List (Low Evidence).
Fetal anomalies v0.4264 UNC13A Zornitza Stark Classified gene: UNC13A as Red List (low evidence)
Fetal anomalies v0.4264 UNC13A Zornitza Stark Gene: unc13a has been classified as Red List (Low Evidence).
Fetal anomalies v0.4263 SYT2 Zornitza Stark Marked gene: SYT2 as ready
Fetal anomalies v0.4263 SYT2 Zornitza Stark Gene: syt2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4263 SYT2 Zornitza Stark Classified gene: SYT2 as Green List (high evidence)
Fetal anomalies v0.4263 SYT2 Zornitza Stark Gene: syt2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4262 SLC25A1 Zornitza Stark Marked gene: SLC25A1 as ready
Fetal anomalies v0.4262 SLC25A1 Zornitza Stark Gene: slc25a1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4262 SLC25A1 Zornitza Stark Phenotypes for gene: SLC25A1 were changed from ?Myasthenic syndrome, congenital, 23, presynaptic MIM#618197; Combined D-2- and L-2-hydroxyglutaric aciduria MIM#615182 to Myasthenic syndrome, congenital, 23, presynaptic MIM#618197; Combined D-2- and L-2-hydroxyglutaric aciduria MIM#615182
Fetal anomalies v0.4261 SLC25A1 Zornitza Stark Classified gene: SLC25A1 as Red List (low evidence)
Fetal anomalies v0.4261 SLC25A1 Zornitza Stark Gene: slc25a1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4260 NHS Zornitza Stark Publications for gene: NHS were set to
Fetal anomalies v0.4259 RPH3A Zornitza Stark Marked gene: RPH3A as ready
Fetal anomalies v0.4259 RPH3A Zornitza Stark Gene: rph3a has been classified as Red List (Low Evidence).
Fetal anomalies v0.4259 RPH3A Zornitza Stark Classified gene: RPH3A as Red List (low evidence)
Fetal anomalies v0.4259 RPH3A Zornitza Stark Gene: rph3a has been classified as Red List (Low Evidence).
Fetal anomalies v0.4258 NHEJ1 Zornitza Stark changed review comment from: Clinical presentation is with SCID, short stature and microcephaly. ID was part of the phenotype in only one individual in the original paper describing this condition.; to: Clinical presentation is with SCID, short stature and microcephaly.
Fetal anomalies v0.4258 NHEJ1 Zornitza Stark edited their review of gene: NHEJ1: Changed rating: GREEN
Fetal anomalies v0.4258 PLEC Zornitza Stark Marked gene: PLEC as ready
Fetal anomalies v0.4258 PLEC Zornitza Stark Gene: plec has been classified as Green List (High Evidence).
Fetal anomalies v0.4258 PLEC Zornitza Stark Classified gene: PLEC as Green List (high evidence)
Fetal anomalies v0.4258 PLEC Zornitza Stark Gene: plec has been classified as Green List (High Evidence).
Fetal anomalies v0.4257 NDUFAF5 Zornitza Stark edited their review of gene: NDUFAF5: Changed rating: GREEN
Fetal anomalies v0.4257 NDUFAF5 Zornitza Stark Deleted their comment
Fetal anomalies v0.4257 LAMA5 Zornitza Stark Marked gene: LAMA5 as ready
Fetal anomalies v0.4257 LAMA5 Zornitza Stark Gene: lama5 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4257 LAMA5 Zornitza Stark Classified gene: LAMA5 as Red List (low evidence)
Fetal anomalies v0.4257 LAMA5 Zornitza Stark Gene: lama5 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4256 NBN Zornitza Stark Deleted their comment
Fetal anomalies v0.4256 NBN Zornitza Stark edited their review of gene: NBN: Changed rating: GREEN
Fetal anomalies v0.4256 NACC1 Zornitza Stark Deleted their comment
Fetal anomalies v0.4256 NACC1 Zornitza Stark edited their review of gene: NACC1: Changed rating: GREEN
Atypical Haemolytic Uraemic Syndrome_MPGN v0.40 TSEN2 Chirag Patel Classified gene: TSEN2 as Green List (high evidence)
Atypical Haemolytic Uraemic Syndrome_MPGN v0.40 TSEN2 Chirag Patel Gene: tsen2 has been classified as Green List (High Evidence).
Atypical Haemolytic Uraemic Syndrome_MPGN v0.39 TSEN2 Chirag Patel gene: TSEN2 was added
gene: TSEN2 was added to Atypical Haemolytic Uraemic Syndrome_MPGN. Sources: Literature
Mode of inheritance for gene: TSEN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TSEN2 were set to PMID: 34964109
Phenotypes for gene: TSEN2 were set to TRACK syndrome
Review for gene: TSEN2 was set to GREEN
Added comment: Biallelic variants in TSEN2 cause pontocerebellar hypoplasia. Canpolat et a. (2022) report an intronic recessive founder variant in TSEN2 that results in abnormal splicing of the mRNA of this gene, in 6 individuals from 4 consanguineous families. Individuals were affected with microcephaly, craniofacial malformations, CNS abnormalities, cognitive retardation of variable severity, and all individuals developed atypical hemolytic uremic syndrome (aHUS) with thrombotic microangiopathy, microangiopathic hemolytic anemia, thrombocytopenia, proteinuria, severe hypertension, and end-stage kidney disease (ESKD) early in life. Bulk RNA sequencing of peripheral blood cells of 4 affected individuals revealed abnormal tRNA transcripts, indicating an alteration of the tRNA biogenesis. Morpholino-mediated skipping of exon 10 of tsen2 in zebrafish produced phenotypes similar to human patients. Proposed as TRACK syndrome (TSEN2 Related Atypical hemolytic uremic syndrome, Craniofacial malformations, Kidney failure).
Sources: Literature
Microcephaly v1.107 TSEN2 Chirag Patel Classified gene: TSEN2 as Green List (high evidence)
Microcephaly v1.107 TSEN2 Chirag Patel Gene: tsen2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4256 D2HGDH Chloe Stutterd gene: D2HGDH was added
gene: D2HGDH was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: D2HGDH was set to BIALLELIC, autosomal or pseudoautosomal
Review for gene: D2HGDH was set to GREEN
Added comment: Antenatal features: macrocephaly, enlarged cerebral ventricles, micrognathia
Sources: Literature
Microcephaly v1.107 TSEN2 Chirag Patel Classified gene: TSEN2 as Green List (high evidence)
Microcephaly v1.107 TSEN2 Chirag Patel Gene: tsen2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4256 COLGALT1 Chloe Stutterd gene: COLGALT1 was added
gene: COLGALT1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: COLGALT1 was set to BIALLELIC, autosomal or pseudoautosomal
Added comment: Antenatal features: porencephalic cyst, calcifications
Sources: Literature
Microcephaly v1.106 TSEN2 Chirag Patel reviewed gene: TSEN2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v0.4256 C2orf69 Chloe Stutterd gene: C2orf69 was added
gene: C2orf69 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: C2orf69 was set to BIALLELIC, autosomal or pseudoautosomal
Review for gene: C2orf69 was set to GREEN
Added comment: Antenatal features: microcephaly, thin CC, Dandy-Walker malformation
Sources: Literature
Fetal anomalies v0.4256 ABHD16A Chloe Stutterd gene: ABHD16A was added
gene: ABHD16A was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ABHD16A was set to BIALLELIC, autosomal or pseudoautosomal
Added comment: Antenatal features: thin CC, joint contractures/foot deformity
Sources: Literature
Fetal anomalies v0.4256 PPP2R3C Chirag Patel Classified gene: PPP2R3C as Green List (high evidence)
Fetal anomalies v0.4256 PPP2R3C Chirag Patel Gene: ppp2r3c has been classified as Green List (High Evidence).
Fetal anomalies v0.4255 PPP2R3C Chirag Patel gene: PPP2R3C was added
gene: PPP2R3C was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PPP2R3C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPP2R3C were set to PMID: 30893644, 34714774, 34750818
Phenotypes for gene: PPP2R3C were set to Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy, OMIM # 618419
Review for gene: PPP2R3C was set to GREEN
Added comment: Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy (GDRM) is characterized by 46,XY complete gonadal dysgenesis in association with extragonadal anomalies, low birth weight, typical facial gestalt, rod and cone dystrophy, sensorineural hearing loss, omphalocele, anal atresia, renal agenesis, skeletal abnormalities, dry and scaly skin, severe myopathy, and neuromotor delay. 11 unrelated families with syndromic complete gonadal dysgenesis. 9 families had 46,XY females with complete gonadal dysgenesis, but 2 families had 46,XX patients with hypergonadotropic hypogonadism, nonvisualized gonads, primary amenorrhea, and absence of secondary sexual characteristics. Variants segregated with disease in each family and were not found in ethnically matched controls or in public variant databases. The heterozygous fathers exhibited morphologic abnormalities of spermatozoa and reduced fertility.
Sources: Literature
Differences of Sex Development v0.241 PPP2R3C Chirag Patel Classified gene: PPP2R3C as Green List (high evidence)
Differences of Sex Development v0.241 PPP2R3C Chirag Patel Gene: ppp2r3c has been classified as Green List (High Evidence).
Differences of Sex Development v0.240 PPP2R3C Chirag Patel gene: PPP2R3C was added
gene: PPP2R3C was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: PPP2R3C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPP2R3C were set to PMID: 30893644, 34714774, 34750818
Phenotypes for gene: PPP2R3C were set to Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy, OMIM # 618419
Review for gene: PPP2R3C was set to GREEN
Added comment: Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy (GDRM) is characterized by 46,XY complete gonadal dysgenesis in association with extragonadal anomalies, low birth weight, typical facial gestalt, rod and cone dystrophy, sensorineural hearing loss, omphalocele, anal atresia, renal agenesis, skeletal abnormalities, dry and scaly skin, severe myopathy, and neuromotor delay.

11 unrelated families with syndromic complete gonadal dysgenesis. 9 families had 46,XY females with complete gonadal dysgenesis, but 2 families had 46,XX patients with hypergonadotropic hypogonadism, nonvisualized gonads, primary amenorrhea, and absence of secondary sexual characteristics. Variants segregated with disease in each family and were not found in ethnically matched controls or in public variant databases. The heterozygous fathers exhibited morphologic abnormalities of spermatozoa and reduced fertility.
Sources: Literature
Fetal anomalies v0.4254 CDX2 Chirag Patel Classified gene: CDX2 as Green List (high evidence)
Fetal anomalies v0.4254 CDX2 Chirag Patel Gene: cdx2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4254 CDX2 Chirag Patel Classified gene: CDX2 as Green List (high evidence)
Fetal anomalies v0.4254 CDX2 Chirag Patel Gene: cdx2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4253 CDX2 Chirag Patel reviewed gene: CDX2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29177441, 34671974; Phenotypes: Congenital abnormalities of anus, renal and urogenital system, vertebrae and/or the limbs; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11072 CDX2 Chirag Patel Classified gene: CDX2 as Green List (high evidence)
Mendeliome v0.11072 CDX2 Chirag Patel Gene: cdx2 has been classified as Green List (High Evidence).
Mendeliome v0.11071 CDX2 Chirag Patel edited their review of gene: CDX2: Added comment: 9 families, with heterozygous variants identified with WES, presenting with congenital abnormalities affecting the development of the anus, the renal and urogenital system, the vertebrae and/or the limbs in varying sequences and severity (incl. sirenomelia and persistent cloaca). A recurrent pathogenic missense variant in the HOX domain of the protein p.(Arg237His) was found in 3 unrelated families. In the mouse cdx2 is essential for anteroposterior patterning of embryonal axis and morphogenesis of cloacal structures. Cdx2 heterozygous conditional mutant mice show a variable phenotype (including imperforate anus, sirenomelia, posterior vertebral truncations, and bladder anomalies).; Changed rating: GREEN; Changed publications: PMID: 29177441, 34671974; Changed phenotypes: Congenital abnormalities of anus, renal and urogenital system, vertebrae and/or the limbs; Set current diagnostic: yes
Microcephaly v1.106 CHKA Konstantinos Varvagiannis gene: CHKA was added
gene: CHKA was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CHKA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHKA were set to 35202461
Phenotypes for gene: CHKA were set to Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature
Penetrance for gene: CHKA were set to Complete
Review for gene: CHKA was set to GREEN
Added comment: Klöckner (2022 - PMID: 35202461) describe the phenotype of 6 individuals (from 5 unrelated families) harboring biallelic CHKA variants.

Shared features incl. abnormal muscle tone(6/6 - hypertonia or hypotonia, 3/6 each), DD/ID (6/6,severe in 4, severe/profound in 2), epilepsy (6/6 - onset: infancy - 3y2m | epileptic spasms or GS at onset), microcephaly (6/6), movement disorders (3/6 - incl. dyskinesia, rigidity, choreoatetotic movements). 2/5 individuals exhibited MRI abnormalities, notably hypomyelination. Short stature was observed in 4/6.

Eventual previous genetic testing was not discussed.

Exome sequencing (quattro ES for 2 sibs, trio ES for 1 individual, singleton for 3 probands) revealed biallelic CHKA variants in all affected individuals. Sanger sequencing was performed for confirmation and segregation studies.

Other variants (in suppl.) were not deemed to be causative for the neurodevelopmental phenotype.

3 different missense, 1 start-loss and 1 truncating variant were identified, namely (NM_0012772.2):
- c.421C>T/p.(Arg141Trp) [3 hmz subjects from 2 consanguineous families],
- c.580C>T/p.Pro194Ser [1 hmz individual born to consanguineous parents],
- c.2T>C/p.(Met1?) [1 hmz individual born to related parents],
- c.14dup/p.(Cys6Leufs*19) in trans with c.1021T>C/p.(Phe341Leu) in 1 individual.

CHKA encodes choline kinase alpha, an enzyme catalyzing the first step of phospholipid synthesis in the Kennedy pathway. The pathway is involved in de novo synthesis of glycerophospholipids, phosphatidylcholine and phosphatidylethanolamine being the most abundant in eukaryotic membranes.

CHKA with its paralog (CHKB) phosphorylates either choline or ethanolamine to phosphocholine or phosphoethanolamine respectively with conversion of ATP to ADP.

As the authors comment, biallelic pathogenic variants in CHKB cause a NDD with muscular dystrophy, hypotonia, ID, microcephaly and structural mitochondrial anomalies (MIM 602541). [Prominent mitochondrial patterning was observed in a single muscle biopsy available from an individual with biallelic CHKA variants].

Other disorders of the Kennedy pathway (due to biallelic PCYT2, SELENOI, PCYT1A variants) present with overlapping features incl. variable DD/ID (no-severe), microcephaly, seizures, visual impairment etc.

CHKA variants were either absent or observed once in gnomAD, affected highly conserved AAs with multiple in silico predictions in favor of a deleterious effect.

In silico modeling suggests structural effects for several of the missense variants (Arg141Trp, Pro194Ser presumably affect ADP binding, Phe341 lying close to the binding site of phosphocholine).

Each of the missense variants was expressed in yeast cells and W. Blot suggested expression at the expected molecular weight at comparative levels. The 3 aforementioned variants exhibited reduced catalytic activity (20%, 15%, 50% respectively).

NMD is thought to underly the deleterious effect of the frameshift one (not studied).

The start-loss variant is expected to result in significantly impaired expression and protein function as eventual utilization of the next possible start codon - occurring at position 123 - would remove 26% of the protein.

Chka(-/-) is embryonically lethal in mice, suggesting that complete loss is not compatible with life. Reduction of choline kinase activity by 30% in heterozygous mice did not appear to result in behavioral abnormalities although this was not studied in detail (PMID cited: 18029352). Finally, screening of 1566 mouse lines identified 198 genes whose disruption yields neuroanatomical phenotypes, Chka(+/-) mice being among these (PMID cited: 31371714).

There is no associated phenotype in OMIM, Gene2Phenotype or SysID.

Overall this gene can be considered for inclusion in the ID and epilepsy panes with green or amber rating (>3 individuals, >3 variants, variant studies, overlapping phenotype of disorders belonging to the same pathway, etc). Consider also inclusion in the microcephaly panel (where available this seemed to be of postnatal onset).
Sources: Literature
Genetic Epilepsy v0.1451 CHKA Konstantinos Varvagiannis gene: CHKA was added
gene: CHKA was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CHKA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHKA were set to 35202461
Phenotypes for gene: CHKA were set to Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature
Penetrance for gene: CHKA were set to Complete
Review for gene: CHKA was set to GREEN
Added comment: Klöckner (2022 - PMID: 35202461) describe the phenotype of 6 individuals (from 5 unrelated families) harboring biallelic CHKA variants.

Shared features incl. abnormal muscle tone(6/6 - hypertonia or hypotonia, 3/6 each), DD/ID (6/6,severe in 4, severe/profound in 2), epilepsy (6/6 - onset: infancy - 3y2m | epileptic spasms or GS at onset), microcephaly (6/6), movement disorders (3/6 - incl. dyskinesia, rigidity, choreoatetotic movements). 2/5 individuals exhibited MRI abnormalities, notably hypomyelination. Short stature was observed in 4/6.

Eventual previous genetic testing was not discussed.

Exome sequencing (quattro ES for 2 sibs, trio ES for 1 individual, singleton for 3 probands) revealed biallelic CHKA variants in all affected individuals. Sanger sequencing was performed for confirmation and segregation studies.

Other variants (in suppl.) were not deemed to be causative for the neurodevelopmental phenotype.

3 different missense, 1 start-loss and 1 truncating variant were identified, namely (NM_0012772.2):
- c.421C>T/p.(Arg141Trp) [3 hmz subjects from 2 consanguineous families],
- c.580C>T/p.Pro194Ser [1 hmz individual born to consanguineous parents],
- c.2T>C/p.(Met1?) [1 hmz individual born to related parents],
- c.14dup/p.(Cys6Leufs*19) in trans with c.1021T>C/p.(Phe341Leu) in 1 individual.

CHKA encodes choline kinase alpha, an enzyme catalyzing the first step of phospholipid synthesis in the Kennedy pathway. The pathway is involved in de novo synthesis of glycerophospholipids, phosphatidylcholine and phosphatidylethanolamine being the most abundant in eukaryotic membranes.

CHKA with its paralog (CHKB) phosphorylates either choline or ethanolamine to phosphocholine or phosphoethanolamine respectively with conversion of ATP to ADP.

As the authors comment, biallelic pathogenic variants in CHKB cause a NDD with muscular dystrophy, hypotonia, ID, microcephaly and structural mitochondrial anomalies (MIM 602541). [Prominent mitochondrial patterning was observed in a single muscle biopsy available from an individual with biallelic CHKA variants].

Other disorders of the Kennedy pathway (due to biallelic PCYT2, SELENOI, PCYT1A variants) present with overlapping features incl. variable DD/ID (no-severe), microcephaly, seizures, visual impairment etc.

CHKA variants were either absent or observed once in gnomAD, affected highly conserved AAs with multiple in silico predictions in favor of a deleterious effect.

In silico modeling suggests structural effects for several of the missense variants (Arg141Trp, Pro194Ser presumably affect ADP binding, Phe341 lying close to the binding site of phosphocholine).

Each of the missense variants was expressed in yeast cells and W. Blot suggested expression at the expected molecular weight at comparative levels. The 3 aforementioned variants exhibited reduced catalytic activity (20%, 15%, 50% respectively).

NMD is thought to underly the deleterious effect of the frameshift one (not studied).

The start-loss variant is expected to result in significantly impaired expression and protein function as eventual utilization of the next possible start codon - occurring at position 123 - would remove 26% of the protein.

Chka(-/-) is embryonically lethal in mice, suggesting that complete loss is not compatible with life. Reduction of choline kinase activity by 30% in heterozygous mice did not appear to result in behavioral abnormalities although this was not studied in detail (PMID cited: 18029352). Finally, screening of 1566 mouse lines identified 198 genes whose disruption yields neuroanatomical phenotypes, Chka(+/-) mice being among these (PMID cited: 31371714).

There is no associated phenotype in OMIM, Gene2Phenotype or SysID.

Overall this gene can be considered for inclusion in the ID and epilepsy panes with green or amber rating (>3 individuals, >3 variants, variant studies, overlapping phenotype of disorders belonging to the same pathway, etc). Consider also inclusion in the microcephaly panel (where available this seemed to be of postnatal onset).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4507 CHKA Konstantinos Varvagiannis gene: CHKA was added
gene: CHKA was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CHKA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHKA were set to 35202461
Phenotypes for gene: CHKA were set to Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature
Penetrance for gene: CHKA were set to Complete
Review for gene: CHKA was set to GREEN
Added comment: Klöckner (2022 - PMID: 35202461) describe the phenotype of 6 individuals (from 5 unrelated families) harboring biallelic CHKA variants.

Shared features incl. abnormal muscle tone(6/6 - hypertonia or hypotonia, 3/6 each), DD/ID (6/6,severe in 4, severe/profound in 2), epilepsy (6/6 - onset: infancy - 3y2m | epileptic spasms or GS at onset), microcephaly (6/6), movement disorders (3/6 - incl. dyskinesia, rigidity, choreoatetotic movements). 2/5 individuals exhibited MRI abnormalities, notably hypomyelination. Short stature was observed in 4/6.

Eventual previous genetic testing was not discussed.

Exome sequencing (quattro ES for 2 sibs, trio ES for 1 individual, singleton for 3 probands) revealed biallelic CHKA variants in all affected individuals. Sanger sequencing was performed for confirmation and segregation studies.

Other variants (in suppl.) were not deemed to be causative for the neurodevelopmental phenotype.

3 different missense, 1 start-loss and 1 truncating variant were identified, namely (NM_0012772.2):
- c.421C>T/p.(Arg141Trp) [3 hmz subjects from 2 consanguineous families],
- c.580C>T/p.Pro194Ser [1 hmz individual born to consanguineous parents],
- c.2T>C/p.(Met1?) [1 hmz individual born to related parents],
- c.14dup/p.(Cys6Leufs*19) in trans with c.1021T>C/p.(Phe341Leu) in 1 individual.

CHKA encodes choline kinase alpha, an enzyme catalyzing the first step of phospholipid synthesis in the Kennedy pathway. The pathway is involved in de novo synthesis of glycerophospholipids, phosphatidylcholine and phosphatidylethanolamine being the most abundant in eukaryotic membranes.

CHKA with its paralog (CHKB) phosphorylates either choline or ethanolamine to phosphocholine or phosphoethanolamine respectively with conversion of ATP to ADP.

As the authors comment, biallelic pathogenic variants in CHKB cause a NDD with muscular dystrophy, hypotonia, ID, microcephaly and structural mitochondrial anomalies (MIM 602541). [Prominent mitochondrial patterning was observed in a single muscle biopsy available from an individual with biallelic CHKA variants].

Other disorders of the Kennedy pathway (due to biallelic PCYT2, SELENOI, PCYT1A variants) present with overlapping features incl. variable DD/ID (no-severe), microcephaly, seizures, visual impairment etc.

CHKA variants were either absent or observed once in gnomAD, affected highly conserved AAs with multiple in silico predictions in favor of a deleterious effect.

In silico modeling suggests structural effects for several of the missense variants (Arg141Trp, Pro194Ser presumably affect ADP binding, Phe341 lying close to the binding site of phosphocholine).

Each of the missense variants was expressed in yeast cells and W. Blot suggested expression at the expected molecular weight at comparative levels. The 3 aforementioned variants exhibited reduced catalytic activity (20%, 15%, 50% respectively).

NMD is thought to underly the deleterious effect of the frameshift one (not studied).

The start-loss variant is expected to result in significantly impaired expression and protein function as eventual utilization of the next possible start codon - occurring at position 123 - would remove 26% of the protein.

Chka(-/-) is embryonically lethal in mice, suggesting that complete loss is not compatible with life. Reduction of choline kinase activity by 30% in heterozygous mice did not appear to result in behavioral abnormalities although this was not studied in detail (PMID cited: 18029352). Finally, screening of 1566 mouse lines identified 198 genes whose disruption yields neuroanatomical phenotypes, Chka(+/-) mice being among these (PMID cited: 31371714).

There is no associated phenotype in OMIM, Gene2Phenotype or SysID.

Overall this gene can be considered for inclusion in the ID and epilepsy panes with green or amber rating (>3 individuals, >3 variants, variant studies, overlapping phenotype of disorders belonging to the same pathway, etc). Consider also inclusion in the microcephaly panel (where available this seemed to be of postnatal onset).
Sources: Literature
Mendeliome v0.11071 CHKA Konstantinos Varvagiannis gene: CHKA was added
gene: CHKA was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CHKA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHKA were set to 35202461
Phenotypes for gene: CHKA were set to Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature
Penetrance for gene: CHKA were set to Complete
Review for gene: CHKA was set to GREEN
Added comment: Klöckner (2022 - PMID: 35202461) describe the phenotype of 6 individuals (from 5 unrelated families) harboring biallelic CHKA variants.

Shared features incl. abnormal muscle tone(6/6 - hypertonia or hypotonia, 3/6 each), DD/ID (6/6,severe in 4, severe/profound in 2), epilepsy (6/6 - onset: infancy - 3y2m | epileptic spasms or GS at onset), microcephaly (6/6), movement disorders (3/6 - incl. dyskinesia, rigidity, choreoatetotic movements). 2/5 individuals exhibited MRI abnormalities, notably hypomyelination. Short stature was observed in 4/6.

Eventual previous genetic testing was not discussed.

Exome sequencing (quattro ES for 2 sibs, trio ES for 1 individual, singleton for 3 probands) revealed biallelic CHKA variants in all affected individuals. Sanger sequencing was performed for confirmation and segregation studies.

Other variants (in suppl.) were not deemed to be causative for the neurodevelopmental phenotype.

3 different missense, 1 start-loss and 1 truncating variant were identified, namely (NM_0012772.2):
- c.421C>T/p.(Arg141Trp) [3 hmz subjects from 2 consanguineous families],
- c.580C>T/p.Pro194Ser [1 hmz individual born to consanguineous parents],
- c.2T>C/p.(Met1?) [1 hmz individual born to related parents],
- c.14dup/p.(Cys6Leufs*19) in trans with c.1021T>C/p.(Phe341Leu) in 1 individual.

CHKA encodes choline kinase alpha, an enzyme catalyzing the first step of phospholipid synthesis in the Kennedy pathway. The pathway is involved in de novo synthesis of glycerophospholipids, phosphatidylcholine and phosphatidylethanolamine being the most abundant in eukaryotic membranes.

CHKA with its paralog (CHKB) phosphorylates either choline or ethanolamine to phosphocholine or phosphoethanolamine respectively with conversion of ATP to ADP.

As the authors comment, biallelic pathogenic variants in CHKB cause a NDD with muscular dystrophy, hypotonia, ID, microcephaly and structural mitochondrial anomalies (MIM 602541). [Prominent mitochondrial patterning was observed in a single muscle biopsy available from an individual with biallelic CHKA variants].

Other disorders of the Kennedy pathway (due to biallelic PCYT2, SELENOI, PCYT1A variants) present with overlapping features incl. variable DD/ID (no-severe), microcephaly, seizures, visual impairment etc.

CHKA variants were either absent or observed once in gnomAD, affected highly conserved AAs with multiple in silico predictions in favor of a deleterious effect.

In silico modeling suggests structural effects for several of the missense variants (Arg141Trp, Pro194Ser presumably affect ADP binding, Phe341 lying close to the binding site of phosphocholine).

Each of the missense variants was expressed in yeast cells and W. Blot suggested expression at the expected molecular weight at comparative levels. The 3 aforementioned variants exhibited reduced catalytic activity (20%, 15%, 50% respectively).

NMD is thought to underly the deleterious effect of the frameshift one (not studied).

The start-loss variant is expected to result in significantly impaired expression and protein function as eventual utilization of the next possible start codon - occurring at position 123 - would remove 26% of the protein.

Chka(-/-) is embryonically lethal in mice, suggesting that complete loss is not compatible with life. Reduction of choline kinase activity by 30% in heterozygous mice did not appear to result in behavioral abnormalities although this was not studied in detail (PMID cited: 18029352). Finally, screening of 1566 mouse lines identified 198 genes whose disruption yields neuroanatomical phenotypes, Chka(+/-) mice being among these (PMID cited: 31371714).

There is no associated phenotype in OMIM, Gene2Phenotype or SysID.

Overall this gene can be considered for inclusion in the ID and epilepsy panes with green or amber rating (>3 individuals, >3 variants, variant studies, overlapping phenotype of disorders belonging to the same pathway, etc). Consider also inclusion in the microcephaly panel (where available this seemed to be of postnatal onset).
Sources: Literature
Fetal anomalies v0.4253 UNC13A Belinda Chong gene: UNC13A was added
gene: UNC13A was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: UNC13A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: UNC13A were set to 27648472; 28192369
Phenotypes for gene: UNC13A were set to Congenital myasthenia; dyskinesia; autism; developmental delay
Review for gene: UNC13A was set to RED
Added comment: One individual described with biallelic variants in this gene and a myasthenic syndrome; another individual reported with de novo variant in this gene and a different neurological phenotype (abnormal movements, developmental delay and autism).
Sources: Literature
Fetal anomalies v0.4253 SYT2 Belinda Chong gene: SYT2 was added
gene: SYT2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SYT2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SYT2 were set to 25192047; 32776697; 32250532; 30533528
Phenotypes for gene: SYT2 were set to Myasthenic syndrome, congenital, 7, presynaptic, MIM# 616040; Myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive MIM#619461
Review for gene: SYT2 was set to GREEN
gene: SYT2 was marked as current diagnostic
Added comment: Myasthenic syndrome bi-allelic #619461- Decreased fetal movements

Mono-allelic disease, PMID 25192047 and 30533528: dominant missense variants in SYT2 reported as a rare cause of distal motor neuropathy and myasthenic syndrome, manifesting with stable or slowly progressive distal weakness of variable severity along with presynaptic NMJ impairment in three families. These variants are thought to have a dominant-negative effect on synaptic vesicle exocytosis, although the precise pathomechanism remains to be elucidated.

Bi-allelic disease: 32250532 and 32776697, 8 individuals from 6 families, with biallelic loss of function variants in SYT2, clinically manifesting with severe congenital onset hypotonia and weakness, with variable degrees of respiratory involvement. Electrodiagnostic findings consistent with a presynaptic congenital myasthenic syndrome (CMS) in some. Treatment with an acetylcholinesterase inhibitor pursued in 4 indviduals showed clinical improvement with increased strength and function.
Sources: Literature
Fetal anomalies v0.4253 SLC25A1 Belinda Chong gene: SLC25A1 was added
gene: SLC25A1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SLC25A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A1 were set to 26870663; 31527857; 29226520
Phenotypes for gene: SLC25A1 were set to ?Myasthenic syndrome, congenital, 23, presynaptic MIM#618197; Combined D-2- and L-2-hydroxyglutaric aciduria MIM#615182
Review for gene: SLC25A1 was set to RED
gene: SLC25A1 was marked as current diagnostic
Added comment: Neonatal onset.

Green for MIM#618197
Four unrelated families. mild congenital myasthenic syndrome.

Red for MIM#615182
Five infants of two consanguineous Bedouin families of the same tribe homozygous for the same variant with EEG compatible with white matter disorder. Death usually occurs in childhood.
Sources: Literature
Fetal anomalies v0.4253 NHS Alison Yeung Marked gene: NHS as ready
Fetal anomalies v0.4253 NHS Alison Yeung Gene: nhs has been classified as Green List (High Evidence).
Fetal anomalies v0.4253 NHS Alison Yeung Phenotypes for gene: NHS were changed from CATARACT CONGENITAL X-LINKED; NANCE-HORAN SYNDROME to Nance-Horan syndrome, MIM# 302350
Fetal anomalies v0.4252 NHS Alison Yeung Mode of inheritance for gene: NHS 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)
Fetal anomalies v0.4251 RPH3A Belinda Chong gene: RPH3A was added
gene: RPH3A was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: RPH3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RPH3A were set to 29441694
Phenotypes for gene: RPH3A were set to Congenital myasthenic syndrome
Review for gene: RPH3A was set to RED
gene: RPH3A was marked as current diagnostic
Added comment: Only one patient with a complex phenotype that included myasthenia, with compound het missense variants, of which only one variant had plausible functional expression data.
Sources: Literature
Fetal anomalies v0.4251 NHEJ1 Alison Yeung Marked gene: NHEJ1 as ready
Fetal anomalies v0.4251 NHEJ1 Alison Yeung Gene: nhej1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4251 NHEJ1 Alison Yeung Phenotypes for gene: NHEJ1 were changed from Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation 611291 to Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, MIM# 611291; Cernunnos-XLF deficiency MONDO:0012650
Fetal anomalies v0.4250 NHEJ1 Alison Yeung Publications for gene: NHEJ1 were set to