ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.628-7C>A (rs373129248)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001080866 SCV000166236 likely benign Hereditary nonpolyposis colorectal neoplasms 2019-12-31 criteria provided, single submitter clinical testing
Counsyl RCV000411528 SCV000487982 uncertain significance Hereditary nonpolyposis colorectal cancer type 5 2015-12-10 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000588337 SCV000601612 uncertain significance not provided 2019-08-26 criteria provided, single submitter clinical testing
Color RCV000580986 SCV000685510 likely benign Hereditary cancer-predisposing syndrome 2015-04-22 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588337 SCV000695919 uncertain significance not provided 2017-05-26 criteria provided, single submitter clinical testing Variant summary: The MSH6 c.628-7C>A variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a damaging outcome for this variant. 3/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 12/117788 control chromosomes, predominantly observed in the uropean (Non-Finnish) subpopulation at a frequency of 0.00017 (11/64642). This frequency is slightly higher than the estimated maximal expected allele frequency of a pathogenic MSH6 variant (0.0001421), suggesting this is likely a benign polymorphism found primarily in the populations of European (Non-Finnish) origin. This variant has been reported in one patient with Lynch syndrome without strong evidence for or against pathogenicity (Barrow_2010). In ClinVar while one clinical diagnostic laboratory has classified this variant as likely benign, another lab has classified it as VUS, both without evidence for independent evaluation. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance-possibly benign until additional information becomes available.
PreventionGenetics,PreventionGenetics RCV000588337 SCV000805907 likely benign not provided 2017-05-30 criteria provided, single submitter clinical testing
Mendelics RCV000411528 SCV001135792 uncertain significance Hereditary nonpolyposis colorectal cancer type 5 2019-05-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000411528 SCV001302616 uncertain significance Hereditary nonpolyposis colorectal cancer type 5 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

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