ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.593A>C (p.Asp198Ala)

dbSNP: rs1569061786
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel RCV003448335 SCV004176255 likely pathogenic Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2023-12-09 reviewed by expert panel curation NM_001754.5(RUNX1):c.593A>C (p.Asp198Ala) is a missense variant. This variant is completely absent from all population databases with at least 20x coverage for RUNX1 in gnomAD v2.1.1 and v3.1.2 (PM2_supporting). This variant affects an amino acid residue within the RHD domain that is defined as a mutational hotspot by the ClinGen MM-VCEP (PM1). The REVEL score is ≥ 0.88 (0.962) (PP3). Two other missense variants (c.593A>T, p.Asp198Val, ClinVar Variation ID 627342 and c.592G>T (p.Asp198Tyr), CA410207975) in the same codon has been classified as likely pathogenic for Hereditary thrombocytopenia and hematologic cancer predisposition syndrome by the ClinGen MMVCEP (PM5_Supporting). This variant has been reported in a proband with AML, meeting RUNX1-phenotypic criteria (PS4_supporting, internal data from PreventionGenetics). In summary, the clinical significance of this variant is likely pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM1, PM2_supporting, PP3, PM5_supporting, PS4_supporting.
PreventionGenetics, part of Exact Sciences RCV000680424 SCV000807795 likely pathogenic not provided 2021-09-21 criteria provided, single submitter clinical testing

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