ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2635-1G>C (rs267608020)

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 RCV000491490 SCV000580615 pathogenic Hereditary cancer-predisposing syndrome 2017-12-12 criteria provided, single submitter clinical testing Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity;Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;Other strong data supporting pathogenic classification
Invitae RCV001069463 SCV001234628 likely pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-10-08 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in the last intron (intron 15) of the MSH2 gene. While this is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual with clinical features of Lynch syndrome (PMID: 12624141). This variant is also known as IVS15-1G>C in the literature. ClinVar contains an entry for this variant (Variation ID: 428547). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Other variant(s) that disrupt this acceptor splice site have been determined to be pathogenic (PMID: 29690800, Invitae). This suggests that this splice site is clinically-significant, and that variants that disrupt this position are likely to be disease-causing. 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.

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.