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| Mendeliome v2.327 | GAK | Lucy Spencer Classified gene: GAK as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v2.327 | GAK | Lucy Spencer Gene: gak has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v2.326 | GAK |
Lucy Spencer gene: GAK was added gene: GAK was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GAK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GAK were set to 37056996 Phenotypes for gene: GAK were set to neurodevelopmental disorder MONDO:0700092, GAK-related Review for gene: GAK was set to AMBER Added comment: PMID 37056996 performed a systematic survey of de novo variants in genes encoding phosphatase catalytic subunits in rare disease patients in the 100000 genomes project. Table 2 lists says 3 missense were identified in GAK in individuals with developmental delay or macrocephaly however no variant information is provided. The supplemental data for this paper lists 5 missense variants in GAK, it is unclear which if any of these were observed in the above individuals. only 2 of these variants are absent from gnomad, the rest have over 10 hets each. The paper also mentions one de novo frameshift variant in GAK in DECIPHER in an individual with abnormality of the nervous an musculoskeletal systems. DECIPHER also had an addition de novo missense in an individual with a similar phenotype. Sources: Literature |
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| Mendeliome v1.2090 | HOXA11 | Sangavi Sivagnanasundram reviewed gene: HOXA11: Rating: AMBER; Mode of pathogenicity: None; Publications: 11101832; Phenotypes: radioulnar synostosis with amegakaryocytic thrombocytopenia 1 MONDO:0024558; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1125 | THPO | Zornitza Stark edited their review of gene: THPO: Added comment: 5 families reported with bi-allelic variants and thrombocytopenia with progression to pancytopenia, aplastic anemia, and bone marrow failure.; Changed publications: 9425899, 10583217, 32150607, 28466964, 24085763, 28559357, 29191945, 36226497; Changed phenotypes: Thrombocythemia 1, MIM# 187950, Thrombocytopenia 9, MIM# 620478, Amegakaryocytic thrombocytopenia, congenital, 2, MIM# 620481; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.45 | PTPN13 |
Ain Roesley gene: PTPN13 was added gene: PTPN13 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PTPN13 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PTPN13 were set to 35643866 Phenotypes for gene: PTPN13 were set to bone marrow failure syndrome MONDO#0000159, PTPN13-related Review for gene: PTPN13 was set to AMBER gene: PTPN13 was marked as current diagnostic Added comment: 2 families Family A: 3 affecteds only 2 sequenced. Hom for a missense 3/3 Anaemia, 1x thrombocytopaenia, 1x severe neutropaenia, bone marrow with pure red cell aplasia noted that the sibling who wasn't sequenced had normal bone marrow morphology Family B: Chet for a missense and inframe del of 1 amino acid Persistent hypogammaglobulinemia after transplant (at least 14 months after) with normal blood counts and Pre-B ALL with MLL rearrangement In vitro studies of individual variants were LoF, including defective erythroid and megakaryocytic differentiation, consistent with anaemia and thrombocytopaenia reported in family A Sources: Literature |
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| Mendeliome v0.9384 | L3MBTL1 |
Zornitza Stark gene: L3MBTL1 was added gene: L3MBTL1 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: L3MBTL1 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) Publications for gene: L3MBTL1 were set to 23543057; 15123827; 30794780 Phenotypes for gene: L3MBTL1 were set to Affected tissue: myeloid lineages; Phenotype resulting from under expression: lymphoid malignancy Review for gene: L3MBTL1 was set to RED Added comment: Germline variation in this imprinted gene is not currently associated with disease. Somatic deletions of 20q are associated with chronic myeloid malignancies. Aziz et al showed that a single heterozygous 20q deletion consistently resulted in the complete loss of expression of the imprinted genes L3MBTL1 and SGK2, indicative of a pathogenetic role for loss of the active paternally inherited locus. Concomitant loss of both L3MBTL1 and SGK2 dysregulated erythropoiesis and megakaryopoiesis. Sources: Expert Review |
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| Mendeliome v0.9256 | MPL | Zornitza Stark Phenotypes for gene: MPL were changed from Myelofibrosis with myeloid metaplasia, somatic, MIM#2544503; Thrombocythemia 2, MIM#601977, AD, SMu; Thrombocytopenia, congenital amegakaryocytic, MIM#604498, AR to Myelofibrosis with myeloid metaplasia, somatic, MIM#254450; Thrombocythemia 2, MIM#601977, AD, SMu; Thrombocytopenia, congenital amegakaryocytic, MIM#604498, AR | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4406 | HOXA11 | Zornitza Stark Phenotypes for gene: HOXA11 were changed from to Radioulnar synostosis with amegakaryocytic thrombocytopenia 1, MIM# 605432 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4402 | HOXA11 | Zornitza Stark reviewed gene: HOXA11: Rating: AMBER; Mode of pathogenicity: None; Publications: 11101832, 16765069; Phenotypes: Radioulnar synostosis with amegakaryocytic thrombocytopenia 1, MIM# 605432; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3502 | MPL | Zornitza Stark Phenotypes for gene: MPL were changed from to Myelofibrosis with myeloid metaplasia, somatic, MIM#2544503; Thrombocythemia 2, MIM#601977, AD, SMu; Thrombocytopenia, congenital amegakaryocytic, MIM#604498, AR | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3496 | MPL | Chern Lim reviewed gene: MPL: Rating: GREEN; Mode of pathogenicity: None; Publications: 28955303, 26423830; Phenotypes: Myelofibrosis with myeloid metaplasia, somatic, MIM#2544503, Thrombocythemia 2, MIM#601977, AD, SMu, Thrombocytopenia, congenital amegakaryocytic, MIM#604498, AR; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2806 | GFI1B |
Bryony Thompson gene: GFI1B was added gene: GFI1B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GFI1B was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: GFI1B were set to 24325358; 23927492; 28041820; 11825872 Phenotypes for gene: GFI1B were set to Bleeding disorder, platelet-type, 17 MIM#187900 Review for gene: GFI1B was set to GREEN Added comment: Three families with a heterozygous variant and one case with a homozygous variant, with supporting in vitro functional assays. A null mouse model contained erythroid and megakaryocytic precursors arrested in their development. Sources: Literature |
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| Mendeliome v0.2259 | MECOM | Zornitza Stark Phenotypes for gene: MECOM were changed from to Radioulnar synostosis with amegakaryocytic thrombocytopenia 2, MIM#616738 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||