ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1936A>C (p.Arg646=) (rs369582237)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163542 SCV000214100 likely benign Hereditary cancer-predisposing syndrome 2014-07-07 criteria provided, single submitter clinical testing
Color RCV000163542 SCV000686168 likely benign Hereditary cancer-predisposing syndrome 2017-03-08 criteria provided, single submitter clinical testing
GeneDx RCV000418482 SCV000520482 likely benign not specified 2016-08-08 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.
Illumina Clinical Services Laboratory,Illumina RCV000123084 SCV000469723 uncertain significance Lynch syndrome 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000418482 SCV000918055 uncertain significance not specified 2017-12-15 criteria provided, single submitter clinical testing Variant summary: The PMS2 c.1936A>C (p.Arg646Arg) variant involves the alteration of a conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE binding sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 11/276994 control chromosomes (gnomAD) at a frequency of 0.0000397, which does not exceed the estimated maximal expected allele frequency of a pathogenic PMS2 variant (0.0001136). However, this frequency may not be accurate due to the sequencing technology used being unable to distinguish between PMS2 and its many overlapping pseudogenes. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as VUS-possibly benign.
Invitae RCV000524453 SCV000166381 likely benign Hereditary nonpolyposis colon cancer 2017-10-04 criteria provided, single submitter clinical testing
PreventionGenetics RCV000679354 SCV000806191 likely benign not provided 2017-10-12 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.