Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001290696 | SCV001478833 | likely pathogenic | Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | 2024-06-24 | reviewed by expert panel | curation | NM_001754.5(RUNX1):c.486G>C (p.Arg162Ser) is a missense variant which affects at least one of the following hotspot residues within the RHD: R107, K110, A134, R162, R166, S167, R169, G170, K194, T196, D198, R201, R204 (PM1). This variant is a missense change at the same residue (p.Arg162) where a different missense change has been previously established as a likely pathogenic variant (ClinVar ID 376022, 376021) based on MM-VCEP rules for RUNX1 (PM5_Supporting). The c.486G>C variant is the same amino acid change (p.Arg162Ser) as a previously established likely pathogenic variant (ClinVar ID 376019) curated using MM-VCEP rules for RUNX1 (PS1_Moderate). REVEL score=0.818, which is >0.75 threshold. SSF and MES show loss of a putative cryptic donor splice site at c.485 (PP3). 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. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM1, PM5_supporting, PS1_moderate, PM2_supporting, PP3. |
Database of Curated Mutations |
RCV000441948 | SCV000504773 | likely pathogenic | Acute myeloid leukemia | 2014-10-02 | no assertion criteria provided | literature only |