ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.46A>G (p.Lys16Glu) (rs777845808)

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 RCV000221254 SCV000276866 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-13 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000599996 SCV000731506 uncertain significance not specified 2017-03-20 criteria provided, single submitter clinical testing The p.Lys16Glu variant in PMS2 has not been previously reported in the literatur e individuals with Lynch syndrome, but has been reported in ClinVar (Variation I D 232676). It has also been identified in 3/17104 of East Asian chromosomes by t he Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs777845808). Computational prediction tools and conservation analysis suggest t hat the p.Lys16Glu variant may not impact the protein, though this information i s not predictive enough to rule out pathogenicity. In summary, the clinical sign ificance of the p.Lys16Glu variant is uncertain.
Invitae RCV000629695 SCV000750651 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-03-25 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamic acid at codon 16 of the PMS2 protein (p.Lys16Glu). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is present in population databases (rs777845808, ExAC 0.04%). This variant has not been reported in the literature in individuals with PMS2-related disease. ClinVar contains an entry for this variant (Variation ID: 232676). 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"). 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.
GeneKor MSA RCV000221254 SCV000822134 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Color RCV000221254 SCV000909685 uncertain significance Hereditary cancer-predisposing syndrome 2019-09-10 criteria provided, single submitter 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.