ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.2317A>G (p.Ser773Gly) (rs587781489)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129453 SCV000184223 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-29 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000461322 SCV000552064 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-08-29 criteria provided, single submitter clinical testing This sequence change replaces serine with glycine at codon 773 of the PMS2 protein (p.Ser773Gly). The serine residue is moderately conserved and there is a small physicochemical difference between serine and glycine. Although this variant is not present in the population databases (rs587781489, ExAC no frequency), the frequency data is considered unreliable due to the presence of a pseudogene that has strong homology to this region. This variant has not been reported in the literature in individuals with PMS2-related disease. ClinVar contains an entry for this variant (Variation ID: 141094). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on mRNA splicing suggest that this variant may alter mRNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Integrated Genetics/Laboratory Corporation of America RCV000781742 SCV000920030 uncertain significance not specified 2018-02-09 criteria provided, single submitter clinical testing Variant summary: PMS2 c.2317A>G (p.Ser773Gly) results in a non-conservative amino acid change located in the MutL, C-terminal, dimerisation of the encoded protein sequence and five of five in-silico tools predict a damaging effect of the variant on protein function. However, these predictions have yet to be functionally assessed. The variant was absent in 120728 control chromosomes (ExAC). 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.2317A>G in individuals affected with Lynch Syndrome. Multiple clinical diagnostic laboratory submissions via ClinVar (evaluation after 2014) classify the variant as "uncertain significiance." Based on the evidence outlined above, the variant was classified as uncertain significance.

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.