ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.664dup (p.Ser222fs)

dbSNP: rs2146076572
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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 RCV003448407 SCV004176273 pathogenic Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2023-12-09 reviewed by expert panel curation NM_001754.5(RUNX1):c.664dup (p.Ser222fs) is a frameshift variant which affects all biologically relevant isoforms. This variant is predicted to undergo nonsense mediated decay in a gene in which loss-of-function is an established mechanism (frameshift (+) c.98-c.779 as per VCEP specifications) (PVS1). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). This variant is a nonsense/frameshift variant that is downstream of c.98 (PM5_Supporting). 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, PM2_supporting, PM5_supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV001387619 SCV001588291 pathogenic Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2020-02-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser222Phefs*6) in the RUNX1 gene. It is expected to result in an absent or disrupted protein product. 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 has not been reported in the literature in individuals with RUNX1-related conditions. This variant is not present in population databases (ExAC no frequency).

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