ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.457+7G>C (rs781280171)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000425768 SCV000516627 likely benign not specified 2016-11-29 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.
Invitae RCV000467549 SCV000561442 likely benign Hereditary nonpolyposis colorectal neoplasms 2020-10-08 criteria provided, single submitter clinical testing
Color Health, Inc RCV000580489 SCV000685492 likely benign Hereditary cancer-predisposing syndrome 2016-03-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000425768 SCV000917750 uncertain significance not specified 2017-12-07 criteria provided, single submitter clinical testing Variant summary: The MSH6 c.457+7G>C variant involves the alteration of a conserved intronic nucleotide. One in silico tool predicts a damaging outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing (though one tool predicts the disappearance of a cryptic acceptor site). ESE finder predicts that this variant may affect the binding site of the splicing factor SC35. However, these predictions have yet to be confirmed by functional studies. This variant was found in 4/245942 control chromosomes at a frequency of 0.0000163, which does not exceed the estimated maximal expected allele frequency of a pathogenic MSH6 variant (0.0001421). This variant co-occurrs with a likely pathogenic variant MSH6 c.1610_1613delAGTA in an internal specimen. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases; nor evaluated for functional impact by in vivo/vitro studies. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign. Because of the absence of clinical information and the lack of functional studies, the variant is classified as VUS-possibly benign, until additional information becomes available.

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