ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.140_150del (p.Leu47fs)

dbSNP: rs2146413726
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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 RCV002264784 SCV002546465 pathogenic Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2022-07-05 reviewed by expert panel curation NM_001754.5(RUNX1):c.140_150del (p.Leu47fs) is a frameshift variant that is predicted to undergo nonsense mediated decay (PVS1). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). Frameshift variant downstream of c.98 (in transcript NM_001754.5) (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 and PM5_supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV001381113 SCV001579365 pathogenic Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2023-03-01 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu47Glnfs*87) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RUNX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1069299). For these reasons, this variant has been classified as Pathogenic.

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