Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV002264780 | SCV002546361 | likely pathogenic | Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | 2022-01-22 | reviewed by expert panel | curation | The NM_001754.5(RUNX1):c.1088_1094del (p.Gly363fs) variant is a frameshift variant that is predicted to lead to an elongated RUNX1 protein and that is not predicted to result in nonsense-mediated mRNA decay (PVS1_Strong). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). This variant was found to co-segregate with disease in multiple affected family members, with three or four (4) meioses observed in one family/across 1 family (PP1; PMID: 18723428). This variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PS4_Supporting; PMID: 18723428). 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, PS4_Supporting and PP1. |
Bone Marrow Failure laboratory, |
RCV001312237 | SCV001502673 | pathogenic | Myelodysplasia | 2021-01-20 | criteria provided, single submitter | research | This heterozygous, frameshift variant of RUNX1 was identified in a female that was diagnosed with MDS RAEB at age 37 yrs (PMID:18723428). It segregates with the disease in three brothers who have MDS, thrombocytopenia and leukemia, respectively. The following ACMG/AMP criteria were used: PVS1, PM2, PP1 and PP3. |