ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.2007-6C>G (rs376018314)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000199056 SCV000253294 likely benign Hereditary nonpolyposis colon cancer 2019-12-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587224 SCV000697324 likely benign not specified 2019-11-01 criteria provided, single submitter clinical testing Variant summary: PMS2 c.2007-6C>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. 4/5 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 2.7e-05 in 149768 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.2007-6C>G in individuals affected with Lynch Syndrome and no experimental evidence demonstrating an impact on protein function have been reported. Co-occurrences with other pathogenic variants have been reported in multiple internal samples, providing supporting evidence for a benign role. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory cited the variant as likely benign, and one laboratory cited the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.
Counsyl RCV000662636 SCV000785322 uncertain significance Hereditary nonpolyposis colorectal cancer type 4 2017-07-06 criteria provided, single submitter clinical testing

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