ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.115C>A (p.Arg39=)

gnomAD frequency: 0.00001  dbSNP: rs786202334
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165094 SCV000215802 likely benign Hereditary cancer-predisposing syndrome 2014-07-25 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV000233469 SCV000284093 likely benign Hereditary nonpolyposis colorectal neoplasms 2024-01-26 criteria provided, single submitter clinical testing
GeneDx RCV001704201 SCV000530573 likely benign not provided 2020-06-10 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000165094 SCV000689959 likely benign Hereditary cancer-predisposing syndrome 2017-04-24 criteria provided, single submitter clinical testing
Counsyl RCV000663112 SCV000786240 likely benign Lynch syndrome 1 2018-03-26 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000427878 SCV001363059 uncertain significance not specified 2019-12-15 criteria provided, single submitter clinical testing Variant summary: MSH2 c.115C>A alters a conserved nucleotide resulting in a synonymous change. Several computational tools predict a significant impact on normal splicing: Five predict the variant creates a cryptic exonic 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 2.2e-05 in 226718 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.115C>A in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (likely benign, n=3; VUS, n=1). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Myriad Genetics, Inc. RCV000663112 SCV004018271 benign Lynch syndrome 1 2023-03-17 criteria provided, single submitter clinical testing This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001704201 SCV004220937 uncertain significance not provided 2023-08-09 criteria provided, single submitter clinical testing To the best of our knowledge, this variant has not been reported in individuals with MSH2-related conditions in the published literature. The frequency of this variant in the general population, 0.000051 (6/117294 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on MSH2 mRNA splicing yielded predictions that this variant may result in the gain of a cryptic splice site without affecting the natural splice sites . Based on the available information, we are unable to determine the clinical significance of this variant.

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.