ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.21G>C (p.Ser7=) (rs587780726)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000566068 SCV000670757 likely benign Hereditary cancer-predisposing syndrome 2015-11-06 criteria provided, single submitter clinical testing
Color RCV000566068 SCV000686177 likely benign Hereditary cancer-predisposing syndrome 2017-04-28 criteria provided, single submitter clinical testing
GeneDx RCV000436675 SCV000514188 likely benign not specified 2017-12-08 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.
Integrated Genetics/Laboratory Corporation of America RCV000436675 SCV000920055 uncertain significance not specified 2018-09-14 criteria provided, single submitter clinical testing Variant summary: PMS2 c.21G>C (p.Ser7Ser) 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 4.1e-06 in 245430 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.21G>C, has been reported in the literature, however, this report does not provide unequivocal conclusions about association of the variant with Lynch Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and all classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Invitae RCV000123085 SCV000166383 likely benign Lynch syndrome 2014-11-06 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.