ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.367-19A>T (rs730881783)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000580191 SCV000685085 likely benign Hereditary cancer-predisposing syndrome 2016-04-17 criteria provided, single submitter clinical testing
Counsyl RCV000412430 SCV000489597 likely benign Lynch syndrome I 2016-10-25 criteria provided, single submitter clinical testing
GeneDx RCV000160650 SCV000211252 benign not specified 2014-01-29 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Integrated Genetics/Laboratory Corporation of America RCV000160650 SCV000917722 uncertain significance not specified 2018-12-12 criteria provided, single submitter clinical testing Variant summary: MSH2 c.367-19A>T alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 5.1e-05 in 274356 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in MSH2 causing Lynch Syndrome (5.1e-05 vs 0.00057), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.367-19A>T in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cites the variant as likely benign. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.

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.