ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2459-1G>A (rs1060501991)

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
Invitae RCV000465186 SCV000548134 likely pathogenic Lynch syndrome 2016-07-24 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 14 of the MSH2 gene. It is expected to disrupt mRNA splicing and likely results in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with a MSH2-related disease. In summary, donor and acceptor splice site variants are typically truncating (PMID: 16199547), and truncating variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). However, without additional functional and/or genetic data, this variant has been classified as Likely Pathogenic.
University of Washington Department of Laboratory Medicine, University of Washington RCV000465186 SCV000887428 likely pathogenic Lynch syndrome 2018-05-01 criteria provided, single submitter clinical testing MSH2 NM_000251.2:c.2459-1G>A has a 98.7% probability of pathogenicity based on combining prior probability from public data with likelihood ratios of 1.56 and 1.56 to 1, generated from evidence of seeing this as a somatic mutation in two independent tumors without loss of heterozygosity at the MSH2 locus. See Shirts et al 2018, PMID 29887214.

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.