ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.458-8C>G

dbSNP: rs372091232
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001718848 SCV000513677 likely benign not provided 2020-02-29 criteria provided, single submitter clinical testing
Invitae RCV000477540 SCV000561469 likely benign Hereditary nonpolyposis colorectal neoplasms 2023-10-26 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001186159 SCV001352510 likely benign Hereditary cancer-predisposing syndrome 2023-11-22 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000420953 SCV001737758 likely benign not specified 2022-09-27 criteria provided, single submitter clinical testing Variant summary: MSH6 c.458-8C>G alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 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 4e-06 in 249796 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.458-8C>G in individuals affected with Hereditary Nonpolyposis Colorectal Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Co-occurrence with a pathogenic variant has been reported (MSH2 c.34dupG, p.E12fs*70), providing supporting evidence for a benign role. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (likely benign n=2, VUS n=1). Based on the evidence outlined above, the variant was classified as likely benign.
All of Us Research Program, National Institutes of Health RCV003995970 SCV004822615 likely benign Lynch syndrome 2023-12-13 criteria provided, single submitter clinical testing

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