ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2006-2A>G (rs267607991)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076349 SCV000107375 likely pathogenic Lynch syndrome 2019-06-21 reviewed by expert panel curation Interrupts canonical donor splice site
Color Health, Inc RCV000774579 SCV000908323 pathogenic Hereditary cancer-predisposing syndrome 2019-02-28 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001420710 SCV000917706 pathogenic Hereditary nonpolyposis colon cancer 2021-05-05 criteria provided, single submitter clinical testing Variant summary: MSH2 c.2006-2A>G is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Five predict the variant abolishes a canonical 3' acceptor site. At least one publication reports experimental evidence that this variant affects mRNA splicing resulting in exon 13 skipping (example, Ding_2007). The variant was absent in 251336 control chromosomes. c.2006-2A>G has been reported in the literature in individuals affected with Hereditary Nonpolyposis Colorectal Cancer/Lynch syndrome (example, Ding_2007, Morak_2017, Parc_2003). These data indicate that the variant may be associated with disease. One clinical diagnostic laboratory and an expert panel (InSiGHT) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was 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.