Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003448649 | SCV004176256 | likely pathogenic | Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | 2023-12-09 | reviewed by expert panel | curation | The NM_001754.5:c.968del (p.Thr323ArgfsTer5) variant in RUNX1 is a frameshift variant that is not expected to result in nonsense-mediated mRNA decay, but the predicted truncated/altered region is critical for protein function (PVS1_strong). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 in gnomAD v2.1.1 and v3.1.2 (PM2_supporting). This variant was identified in a patient meeting at least one of the RUNX1-phenotypic criteria (PS4_supporting; internal data). The de novo status has been confirmed (PS2_supporting). 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: PVS1_strong, PM2_supporting, PS2_supporting, PS4_supporting. |