ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.270dup (p.Arg91fs)

dbSNP: rs2057999400
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel RCV003448386 SCV004176237 pathogenic Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2023-12-09 reviewed by expert panel curation The NM_001754.5(RUNX1):c.270dup (p.Arg91AlafsTer47) variant in RUNX1 is a frameshift variant predicted to cause a premature stop codon in biologically relevant exon 5/9 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant is absent from gnomAD v2, v3, and v4 with at least 20x coverage (PM2_Supporting). The variant has been reported in a 78yo female with AML, but variant origin is unclear (PMID: 37680325); it has also been reported in 1/3219 patients referred for clinical diagnostic testing who underwent WGS, but phenotype and germline origin are unspecified (PMID: 33726816) (PS4_Supporting is not met). However, other pathogenic/likely pathogenic frameshift alterations in exons 4 or 5 have been reported (PMID: 35764482) (PM5_Supporting). In summary, this variant meets the criteria to be classified as pathogenic for autosomal dominant hereditary thrombocytopenia and hematologic cancer predisposition syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy VCEP: PVS1, PM2_Supporting, and PM5_Supporting. (Version 2; date of approval)
Clinical Genetics and Genomics, Karolinska University Hospital RCV001269762 SCV001450005 pathogenic not provided 2018-01-25 criteria provided, single submitter clinical testing

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.