ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1053del (p.Leu351fs)

dbSNP: rs1554298756
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
Labcorp Genetics (formerly Invitae), Labcorp RCV003758908 SCV004538864 pathogenic Hereditary nonpolyposis colorectal neoplasms 2023-05-03 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 560019). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu351Phefs*5) in the PMS2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816).
All of Us Research Program, National Institutes of Health RCV004807078 SCV005429606 pathogenic Lynch syndrome 2024-04-25 criteria provided, single submitter clinical testing This variant deletes 1 nucleotide in exon 10 of the PMS2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with PMS2-related disorders in the literature. This variant has been reported in individuals affected with breast or lung cancer (PMID: 30376427, 35273153). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of PMS2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Ambry Genetics RCV004944082 SCV005472550 pathogenic Hereditary cancer-predisposing syndrome 2024-10-25 criteria provided, single submitter clinical testing The c.1053delG pathogenic mutation, located in coding exon 10 of the PMS2 gene, results from a deletion of one nucleotide at nucleotide position 1053, causing a translational frameshift with a predicted alternate stop codon (p.L351Ffs*5). This alteration has been reported in individuals with breast and lung cancers (Latham A et al. J Clin Oncol, 2019 Feb;37:286-295; Sun S et al. Front Oncol, 2019 Jun;9:550). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
3DMed Clinical Laboratory Inc RCV000677897 SCV000804058 pathogenic Colon cancer 2017-04-05 no assertion criteria provided 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.