Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV004699592 | SCV005205691 | likely pathogenic | Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | 2024-09-10 | reviewed by expert panel | curation | NM_001754.5(RUNX1):c.965del (p.Ser322Ter) is a nonsense variant located downstream of c.98 in transcript NM_001754.4 (PM5_Supporting). It is not expected to undergo nonsense-mediated decay, and the resulting frameshift affects positions c.759-c.1440 as per VCEP specifications, which are critical for protein function (PVS1_Strong). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). In summary, this variant meets criteria to be classified as likely pathogenic for hereditary thrombocytopenia and hematologic cancer predisposition syndrome based on the ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1_strong, PM2_supporting, PM5_supporting. |
| Labcorp Genetics |
RCV001963364 | SCV002241748 | uncertain significance | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | 2021-11-19 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with RUNX1-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser322*) in the RUNX1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 159 amino acid(s) of the RUNX1 protein. |