ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.164-2A>G

dbSNP: rs587779324
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
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076818 SCV000108272 likely pathogenic Lynch syndrome 2019-06-21 reviewed by expert panel curation Interrupts canonical donor splice site
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV003320559 SCV004025140 likely pathogenic not provided 2023-08-15 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000076818 SCV004843102 likely pathogenic Lynch syndrome 2023-11-27 criteria provided, single submitter clinical testing The c.164-2A>G variant in the PMS2 gene is located at the canonical splice site of intron 2 and is predicted to inflict acceptor loss (SpliceAI delta score: 0.99), resulting in aberrant splicing and disrupted protein product. The variant has been reported in an individual with colorectal cancer, and experimental RNA analysis from patient's lymphocytes showed aberrant transcripts and negative functional impact (PMID: 23709753). Loss-of-function variants in PMS2 are known to be pathogenic (PMID: 28514183, 25512458, 35223509). The variant is reported in ClinVar as likely pathogenic (ID: 91308) and reviewed by the expert panel. The variant is absent in the general population database (gnomAD). Therefore, the c.164-2A>G variant of PMS2 has been classified as likely pathogenic.

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.