ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.2458+8C>G

gnomAD frequency: 0.00003  dbSNP: rs189025757
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000122985 SCV000166273 likely benign Hereditary nonpolyposis colorectal neoplasms 2022-11-03 criteria provided, single submitter clinical testing
Counsyl RCV000411107 SCV000489490 likely benign Lynch syndrome 1 2016-10-11 criteria provided, single submitter clinical testing
GeneDx RCV000202181 SCV000513665 likely benign not specified 2017-07-20 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.
Color Diagnostics, LLC DBA Color Health RCV000580893 SCV000685046 likely benign Hereditary cancer-predisposing syndrome 2015-07-15 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000202181 SCV000919708 uncertain significance not specified 2021-04-28 criteria provided, single submitter clinical testing Variant summary: MSH2 c.2458+8C>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 3/4 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 6.4e-05 in 251096 control chromosomes, predominantly at a frequency of 0.00026 within the Latino subpopulation in the gnomAD database. 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.2458+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 another pathogenic variant has been reported (TP53 c.637C>T, p.Arg213X) in our internal database, providing supporting evidence for a benign role. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000202181 SCV002047332 likely benign not specified 2021-03-24 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000202181 SCV002067214 likely benign not specified 2018-07-17 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000411107 SCV004018346 benign Lynch syndrome 1 2023-03-21 criteria provided, single submitter clinical testing This variant is considered benign. This variant is intronic and is not expected to impact mRNA splicing. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752].
Mayo Clinic Laboratories, Mayo Clinic RCV000202181 SCV000257177 uncertain significance not specified no assertion criteria provided research

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