ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2634+5G>T (rs267608017)

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
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076522 SCV000107552 uncertain significance Lynch syndrome 2013-09-05 reviewed by expert panel research Insufficient evidence (splicing analysis not done in patient RNA)
Invitae RCV000076522 SCV000260295 likely pathogenic Lynch syndrome 2015-08-28 criteria provided, single submitter clinical testing This sequence change falls in intron 15 of the MSH2 mRNA. It does not directly change the encoded amino acid sequence of the MSH2 protein. This variant is not present in population databases and has been reported in an individual with Lynch syndrome (PMID: 18561205). ClinVar also contains an entry for this variant (RCV000076522). Experimental studies based on ex vivo splicing assay demonstrated that this intronic change likely results in exon 15 skipping (PMID: 18561205). A different variant affecting this nucleotide (c.2634+5G>C) has been reported to segregate with colorectal cancer in five affected individuals within a single family (PMID: 18033691). The tumor of the proband in this family was MSI-H and immunohistochemistry indicated a loss of MSH2 protein. Furthermore, cDNA analysis revealed MSH2 exon 15 skipping. This suggests that this nucleotide may be crucial for normal mRNA splicing. For these reasons, 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.