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Mendeliome v2.0 JAK2 Gene migrated from ENSG00000096968 to ENSG00000096968 (gene set migration)
Mendeliome v1.4963 JAK2 Zornitza Stark Phenotypes for gene: JAK2 were changed from Thrombocythaemia 3, MIM# 614521 to Thrombocythaemia 3, MIM# 614521; Familial polycythemia MONDO:0001115, JAK2-related
Mendeliome v1.4962 JAK2 Zornitza Stark Publications for gene: JAK2 were set to 22397670; 35129130; 41053421; 39657124; 39323414
Mendeliome v1.4961 JAK2 Zornitza Stark edited their review of gene: JAK2: Changed phenotypes: Thrombocythaemia 3, MIM# 614521, Familial polycythemia MONDO:0001115, JAK2-related
Mendeliome v1.4961 JAK2 Zornitza Stark changed review comment from: Association with thrombocytosis:

PMID 35764421: Reports 3 individuals from a single family with heterozygous germline JAK2 p.E846D missense variants presenting with adult‑onset erythrocytosis, elevated haemoglobin/haematocrit and no thrombosis.

PMID 38629639: Reports 3 individuals from a single family with a heterozygous germline JAK2 R715T missense gain‑of‑function variant presenting with PV‑like erythrocytosis (elevated Hb, low‑normal EPO, no thrombocytosis/leukocytosis). Detailed clinical data for proband, mother and son are provided, together with in‑vitro luciferase, Ba/F3‑EPOR proliferation, p‑STAT5 and EPO‑independent BFU‑E assays demonstrating increased JAK‑STAT signalling. Ropeg‑IFNα treatment induced remission in proband and mother.; to: Association with erythrocytosis:

PMID 35764421: Reports 3 individuals from a single family with heterozygous germline JAK2 p.E846D missense variants presenting with adult‑onset erythrocytosis, elevated haemoglobin/haematocrit and no thrombosis.

PMID 38629639: Reports 3 individuals from a single family with a heterozygous germline JAK2 R715T missense gain‑of‑function variant presenting with PV‑like erythrocytosis (elevated Hb, low‑normal EPO, no thrombocytosis/leukocytosis). Detailed clinical data for proband, mother and son are provided, together with in‑vitro luciferase, Ba/F3‑EPOR proliferation, p‑STAT5 and EPO‑independent BFU‑E assays demonstrating increased JAK‑STAT signalling. Ropeg‑IFNα treatment induced remission in proband and mother.
Mendeliome v1.4961 JAK2 Zornitza Stark edited their review of gene: JAK2: Added comment: Association with thrombocytosis:

PMID 35764421: Reports 3 individuals from a single family with heterozygous germline JAK2 p.E846D missense variants presenting with adult‑onset erythrocytosis, elevated haemoglobin/haematocrit and no thrombosis.

PMID 38629639: Reports 3 individuals from a single family with a heterozygous germline JAK2 R715T missense gain‑of‑function variant presenting with PV‑like erythrocytosis (elevated Hb, low‑normal EPO, no thrombocytosis/leukocytosis). Detailed clinical data for proband, mother and son are provided, together with in‑vitro luciferase, Ba/F3‑EPOR proliferation, p‑STAT5 and EPO‑independent BFU‑E assays demonstrating increased JAK‑STAT signalling. Ropeg‑IFNα treatment induced remission in proband and mother.; Changed publications: 22397670, 35129130, 41053421, 39657124, 39323414, 35764421, 38629639
Mendeliome v1.4961 JAK2 Zornitza Stark Publications for gene: JAK2 were set to 22397670; 35129130
Mendeliome v1.4960 JAK2 Zornitza Stark Classified gene: JAK2 as Green List (high evidence)
Mendeliome v1.4960 JAK2 Zornitza Stark Gene: jak2 has been classified as Green List (High Evidence).
Mendeliome v1.4959 JAK2 Zornitza Stark edited their review of gene: JAK2: Added comment: PMID 41053421: three individuals with germline c.1691 G > A, p.Arg564Gln (R564Q) gain-of-function variant and thrombocytosis.
PMID 39657124: Reports 12 individuals from 10 families with heterozygous germline JAK2 p.R564Q/L variants presenting with hereditary thrombocythemia (HT) and variable predisposition to myeloproliferative neoplasms (ET, PV) and lymphoid malignancies (CLL, AML, MGUS).
PMID 39323414: Reports 8 individuals from a single family with heterozygous germline JAK2 F556V gain‑of‑function variants presenting with familial thrombocytosis (hereditary thrombocythemia).

Overall, sufficient cases with germline variants for GREEN rating.; Changed rating: GREEN; Changed publications: 22397670, 35129130, 41053421, 39657124, 39323414
Mendeliome v1.1502 SH2B3 Ain Roesley commented on gene: SH2B3: PMID:37206266
2x families
- hom missense variant Val402Met:
functional performed on patient's fibroblasts demonstrated increased basal pSTAT5, pSTAT3 and increased pJAK2 + pSTAT5 after stimulation with IL-3, GH, GM-CSF and EPO

- hom fs Arg148Profs*40
functional performed in zebrafish demonstrated increased number of macrophages and thrombocytes

PMID:23908464;
1 fam with 2 affecteds with dev delay + autoimmunity + (1x) ALL, hom for Asp231Gly fs*3

PMID:38152053;
JMML cohort - 2x hom missense + 2x het PTCs
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 v0.0 JAK2 Zornitza Stark gene: JAK2 was added
gene: JAK2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: JAK2 was set to Unknown