Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001290697 | SCV001478834 | likely pathogenic | Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | 2021-01-12 | reviewed by expert panel | curation | This missense variant has not been reported in gnomAD (v2 and v3) [PM2]. Although it has not been clearly reported as a germline variant (PMID: 28855357, 28927163, 31649132, COSMIC), it is located at a residue that directly contacts DNA (PMID: 11276260, 12377125, 12393679, 12807882, 19808697, 28231333) and is considered a hotspot residue (PMID: 31648317, 27294619, 23958918) [PM1]. Although this variant has not been functionally evaluated, computational evidence supports a deleterious effect of this variant [PP3] and another missense variant at the same residue (i.e. p.R162G) is classified as likely pathogenic by the ClinGen MM-VCEP [PM5_supporting]. In summary, this variant meets criteria to be classified as likely pathogenic. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM1, PM2, PM5_supporting, and PP3. |
Database of Curated Mutations |
RCV000433391 | SCV000504772 | likely pathogenic | Acute myeloid leukemia | 2014-10-02 | no assertion criteria provided | literature only |