ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.592G>A (p.Asp198Asn)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel RCV004701228 SCV005205696 likely pathogenic Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-09-10 reviewed by expert panel curation NM_001754.5(RUNX1):c.592G>A (p.Asp198Asn) is a missense mutation affecting a hotspot residue within the RHD (PM1). This variant is a missense change at the same residue (p.D198) where a different missense change has been previously established as a likely pathogenic variant (ClinVar ID 627342) based on MM-VCEP rules for RUNX1 (PM5_Supporting). This missense variant has a REVEL score ≥ 0.88 (0.93) (PP3). It is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). This variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PS4_Supporting; PMID: 26175287). 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: PM1, PP3, PM2_supporting, PM5_supporting, PS4_supporting.

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