ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1077-7A>G

gnomAD frequency: 0.00006  dbSNP: rs370807334
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000232807 SCV000284090 likely benign Hereditary nonpolyposis colorectal neoplasms 2024-01-17 criteria provided, single submitter clinical testing
GeneDx RCV001705240 SCV000518232 likely benign not provided 2020-03-06 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000417988 SCV000696198 uncertain significance not specified 2019-04-18 criteria provided, single submitter clinical testing Variant summary: MSH2 c.1077-7A>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. 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 1.4e-05 in 280074 control chromosomes (gnomAD). 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.1077-7A>G 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 uncertain significance.
Genetic Services Laboratory, University of Chicago RCV000417988 SCV002066866 uncertain significance not specified 2021-02-15 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV002258835 SCV002528808 likely benign Hereditary cancer-predisposing syndrome 2021-10-09 criteria provided, single submitter curation
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001705240 SCV004220935 uncertain significance not provided 2023-07-27 criteria provided, single submitter clinical testing To the best of our knowledge, this variant has not been reported in the published literature. The frequency of this variant in the general population, 0.00017 (4/24174 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 splicing yielded predictions that this variant does not affect MSH2 mRNA splicing . Based on the available information, we are unable to determine the clinical significance of this variant.
PreventionGenetics, part of Exact Sciences RCV004541370 SCV004784810 likely benign MSH2-related disorder 2020-02-25 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
All of Us Research Program, National Institutes of Health RCV003998749 SCV004818120 likely benign Lynch syndrome 2024-02-05 criteria provided, single submitter clinical testing

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