Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001982958 | SCV004176245 | pathogenic | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | 2023-12-09 | reviewed by expert panel | curation | PVS1: frameshift variant (-1) between c.98-758. PM2_supporting: This variant is completely absent from all population databases with at least 20x coverage for RUNX1. PS4_Supporting: This variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PS4_ Supporting; PMID: 34166225). This variant is a nonsense/frameshift variants that is downstream of c.98 (PM5_Supporting). 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, PM2_supporting, PS4_supporting, PM5_supporting. |
Labcorp Genetics |
RCV001982958 | SCV002238059 | pathogenic | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | 2021-11-11 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with RUNX1-related conditions. For these reasons, this variant has been classified as Pathogenic. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln213Argfs*24) in the RUNX1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RUNX1 are known to be pathogenic (PMID: 18723428, 24100448). |