ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3439-10T>A (rs730881819)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160728 SCV000211362 benign not specified 2014-07-24 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.
Invitae RCV000227561 SCV000283805 likely benign Hereditary nonpolyposis colorectal neoplasms 2020-11-10 criteria provided, single submitter clinical testing
Counsyl RCV000410182 SCV000489332 uncertain significance Hereditary nonpolyposis colorectal cancer type 5 2016-09-19 criteria provided, single submitter clinical testing
Color Health, Inc RCV000580444 SCV000685403 likely benign Hereditary cancer-predisposing syndrome 2015-12-28 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000160728 SCV000917735 uncertain significance not specified 2021-02-22 criteria provided, single submitter clinical testing Variant summary: MSH6 c.3439-10T>A alters a 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 2e-05 in 251432 control chromosomes, predominantly at a frequency of 0.00025 within the African or African-American 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.3439-10T>A in individuals affected with Hereditary Nonpolyposis Colorectal Cancer and no experimental evidence demonstrating its impact on protein function have been reported. However, one database (UMD) cites the variant as having normal splicing via RT-PCR, without evidence to independently evaluate. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Two submitters classified the variant as likely benign while one classified the variand as VUS. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.

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