ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.861C>A (p.Tyr287Ter)

dbSNP: rs121912499
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel RCV004595487 SCV000965614 pathogenic Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-03-26 reviewed by expert panel curation The NM_001754.4:c.861C>A (p.Tyr287Ter) variant is a nonsense variant that is predicted to introduce a premature stop codon and expected to result in nonsense-mediated mRNA decay (PVS1). This variant was found to co-segregate with disease in multiple affected family members, with seven meioses observed in one family (PP1_Strong; PMID: 11830488). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). This variant is a nonsense/frameshift variants that is downstream of c.98 (PM5_Supporting). The variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PS4_ Supporting; PMID: 11830488). 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, PP1_Strong, PM2_supporting, PS4_Supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV000015553 SCV001399806 pathogenic Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2021-11-06 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: 14467). This variant is also known as Y260X. This premature translational stop signal has been observed in individual(s) with familial platelet disorder with associated myeloid malignancy (PMID: 11830488). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr287*) 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).
OMIM RCV000015553 SCV000035818 pathogenic Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2002-02-15 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.