Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001078212 | SCV001244321 | likely pathogenic | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | 2020-01-14 | reviewed by expert panel | curation | The NM_001754.4:c.506G>T (p.Arg169Ile) variant affects one of the hotspot residues established by the MM-VCEP for RUNX1 (PM1). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2). It was found to co-segregate with disease in multiple affected family members, with four meioses observed in one family (PP1; from internal laboratory data). This missense variant has a REVEL score >0.75 (0.939) (PP3). This variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PS4_ Supporting; from internal laboratory data). In summary, this variant meets criteria to be classified as likely pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM1, PM2, PP1, PP3, PS4_Supporting. |