ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.828C>A (p.Cys276Ter)

dbSNP: rs757324104
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000487083 SCV000570596 pathogenic not provided 2016-06-08 criteria provided, single submitter clinical testing This variant is denoted PMS2 c.828C>A at the cDNA level and p.Cys276Ter (C276X) at the protein level. The substitution creates a nonsense variant, which changes a Cysteine to a premature stop codon (TGC>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, it is considered pathogenic.
Invitae RCV000818334 SCV000958941 pathogenic Hereditary nonpolyposis colorectal neoplasms 2023-05-10 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 421403). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This sequence change creates a premature translational stop signal (p.Cys276*) 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).
Ambry Genetics RCV002431407 SCV002677245 pathogenic Hereditary cancer-predisposing syndrome 2022-10-06 criteria provided, single submitter clinical testing The p.C276* pathogenic mutation (also known as c.828C>A), located in coding exon 8 of the PMS2 gene, results from a C to A substitution at nucleotide position 828. This changes the amino acid from a cysteine to a stop codon within coding exon 8. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
Myriad Genetics, Inc. RCV003449212 SCV004187676 pathogenic Lynch syndrome 4 2023-09-19 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.

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