ClinVar Miner

Submissions for variant NM_001754.4(RUNX1):c.610C>T (p.Arg204Ter) (rs1569061768)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel RCV001374725 SCV001571654 pathogenic Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2021-01-11 reviewed by expert panel curation The c.610C>T (Arg204Ter) variant is a nonsense variant that is predicted to introduce a premature stop codon in exon 5/8 and expected to result in nonsense-mediated mRNA decay (PVS1). It is completely absent from gnomAD v2.1.1 and v3 with at least 20x coverage for RUNX1 (PM2). This variant has been reported in three probands meeting at least one of the RUNX1- phenotypic criteria (PS4_Moderate; PMID: 32165484, 10508512, 26492932). It was also found to co-segregate with disease in multiple affected family members, with eight meioses observed in across 3 families (PP1_Strong; PMID: 10508512, 26492932 , 32165484). In summary, this variant meets criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1, PP1_Strong, PS4_Moderate, PM2.
PreventionGenetics,PreventionGenetics RCV000680426 SCV000807797 pathogenic not provided 2014-01-03 criteria provided, single submitter clinical testing
Invitae RCV000799444 SCV000939106 pathogenic Familial platelet disorder with associated myeloid malignancy 2018-08-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg204*) in the RUNX1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with familial platelet disorder with predisposition to acute myelogenous leukemia in a family (PMID: 10508512). Loss-of-function variants in RUNX1 are known to be pathogenic (PMID: 18723428, 24100448). For these reasons, this variant has been classified as Pathogenic.
Biochemical Molecular Genetic Laboratory,King Abdulaziz Medical City RCV000799444 SCV001133125 pathogenic Familial platelet disorder with associated myeloid malignancy 2019-09-26 no assertion criteria provided clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge RCV001003539 SCV001161867 likely pathogenic Thrombocytopenia no assertion criteria provided research

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