ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.943-1G>T (rs12476364)

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
Ambry Genetics RCV000491423 SCV000580403 pathogenic Hereditary cancer-predisposing syndrome 2017-05-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Other strong data supporting pathogenic classification,Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity
Invitae RCV000468897 SCV000548146 pathogenic Hereditary nonpolyposis colon cancer 2018-12-10 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 5 of the MSH2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several families with suspected Lynch syndrome (PMID: 28874130). ClinVar contains an entry for this variant (Variation ID: 408461). Different variants affecting this nucleotide (c.943-1G>A and c.943-1G>C) have been reported in the literature in individuals affected with Lynch syndrome (PMID: 11151427, 20233461, 26866578, 15849733). This suggests that this nucleotide is important for normal RNA splicing, and that other variants at this position may also be pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic.

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.