Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
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Clin |
RCV003448646 | SCV004176244 | pathogenic | Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | 2023-12-09 | reviewed by expert panel | curation | NC_000021.9:g.(?_34880547)_(34880723_?)del causes a deletion of exon 5 in RUNX1, which results in a frameshift mutation leading to nonsense mediated decay of the protein. A similar deletion was found to co-segregate with disease in multiple affected family members, with five meioses observed in one family (PP1_ Moderate; PMID: 19946261). Deletions of exon 5 have been reported in two probands meeting at least one of the RUNX1-phenotypic criteria (PS4_ Moderate; PMID: 19946261, PMID: 32990483). Exon 5 contains codons 118 to 170 which lie within the functional domain of RUNX1. In addition, the deletion is absent from population databases. In summary, this variant meets criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1, PP1_moderate, PS4_moderate, PM1_supporting, PM2_supporting. |