ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1394A>G (p.Lys465Arg) (rs141084758)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165567 SCV000216301 likely benign Hereditary cancer-predisposing syndrome 2018-04-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign),Other strong data supporting benign classification
Color RCV000165567 SCV000911285 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-04 criteria provided, single submitter clinical testing
Counsyl RCV000662635 SCV000785320 uncertain significance Hereditary nonpolyposis colorectal cancer type 4 2017-07-06 criteria provided, single submitter clinical testing
Invitae RCV000546976 SCV000625521 uncertain significance Hereditary nonpolyposis colon cancer 2018-12-22 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 465 of the PMS2 protein (p.Lys465Arg). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and arginine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with a PMS2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant has uncertain impact on PMS2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of 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.