Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003448334 | SCV004176252 | likely pathogenic | Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | 2023-12-09 | reviewed by expert panel | curation | The c.582A>C (p.Lys194Asn) variant affects one of the hotspot residues within the Runt homology domain established by the MM-VCEP for RUNX1 (PM1). This variant is completely absent from all population databases (gnomAD v2.1.1 and v3) with at least 20x coverage for RUNX1 (PM2). This missense variant has a REVEL score of 0.826 that is >0.75 (PP3). This variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PS4_ Supporting; PMIDs: 27210295, 28659335, 31309983). 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, PP3, PS4_Supporting. |
Prevention |
RCV000680423 | SCV000807794 | uncertain significance | not provided | 2016-03-22 | criteria provided, single submitter | clinical testing |