ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.847C>T (p.Gln283Ter)

dbSNP: rs374341207
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel RCV003448452 SCV004176235 pathogenic Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2023-12-09 reviewed by expert panel curation The NM_001754.5(RUNX1):c.847C>T (p.Gln283Ter) is a nonsense variant that is predicted to cause a premature stop codon in a gene in which loss-of-function is an established mechanism (nonsense c.98-c.916 as per VCEP specifications) (PVS1).This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). This nonsense variant is downstream of c.98 in transcript NM_001754.4 (PM5_Supporting). In summary, this variant meets the criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1, PM2_supporting, PM5_supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV002254234 SCV004311173 pathogenic Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2023-08-03 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1691248). This variant has not been reported in the literature in individuals affected with RUNX1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln283*) in the RUNX1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RUNX1 are known to be pathogenic (PMID: 18723428, 24100448).
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology RCV002254234 SCV002525485 pathogenic Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 no assertion criteria provided research

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