ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.508+2T>C

dbSNP: rs1601515707
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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 RCV001195662 SCV001366058 pathogenic Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-09-10 reviewed by expert panel curation The NM_001754.4:c.508+2T>C variant is a donor splice site variant that is predicted to introduce a premature stop codon and expected to result in nonsense-mediated mRNA decay (PVS1). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). This variant is downstream of c.98 (PM5_supporting). Two patients reported with this variant in the literature do not meet criteria for PS4 (PMID: 30520015; 29296763). 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 RCV000796520 SCV000936038 likely pathogenic Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2021-12-30 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 642956). 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 affects a donor splice site in intron 5 of the RUNX1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in RUNX1 are known to be pathogenic (PMID: 18723428, 24100448).
Fulgent Genetics, Fulgent Genetics RCV002495048 SCV002803289 likely pathogenic Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1; Acute myeloid leukemia 2021-08-04 criteria provided, single submitter clinical testing

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