ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.289_299delinsCTCCTTCCGCTG (p.Phe97fs)

dbSNP: rs1601528701
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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 RCV003448349 SCV004176279 pathogenic Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2023-12-09 reviewed by expert panel curation NM_001754.5(RUNX1):c.289_299delinsCTCCTTCCGCTG (p.Phe97fs) is a frameshift variant. The transcript product is predicted to undergo NMD (PVS1). 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 was reported in ClinVar in 2018 by Invitae but the affected status of the proband is unknown (Variation ID 647118). This variant is a frameshift change or agreement in splicing predictors (SSF and MES) showing no splicing effects (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 RCV000801548 SCV000941327 pathogenic Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2018-09-18 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with RUNX1-related disease. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in RUNX1 are known to be pathogenic (PMID: 18723428, 24100448). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Phe97Leufs*41) in the RUNX1 gene. It is expected to result in an absent or disrupted protein product.

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