Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000590029 | SCV000697311 | likely pathogenic | Lynch syndrome | 2016-04-13 | criteria provided, single submitter | clinical testing | Variant summary: Variant affects a non-conserved nucleotide and results in a nonsense mutation predicted to cause a loss of normal protein function due to production of a truncated protein or by the absence of the protein product due to nonsense-mediated mRNA decay. It is absent from the large and broad cohorts of the ExAC project and to our knowledge, it was not reported in affected individuals either. Loss of function of PMS2 is a known mechanism of Lynch syndrome (GeneReviews), therefore, this nonsense variant was classified as Likely Pathogenic. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000759915 | SCV000889612 | likely pathogenic | not provided | 2018-01-12 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001219508 | SCV001391451 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-09-06 | 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: 496033). 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.Gln637*) 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 | RCV002413666 | SCV002720538 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-05-23 | criteria provided, single submitter | clinical testing | The p.Q637* pathogenic mutation (also known as c.1909C>T), located in coding exon 11 of the PMS2 gene, results from a C to T substitution at nucleotide position 1909. This changes the amino acid from a glutamine to a stop codon within coding exon 11. 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, |
RCV003451332 | SCV004187780 | pathogenic | Lynch syndrome 4 | 2023-09-21 | 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. |
| Baylor Genetics | RCV003451332 | SCV004207903 | likely pathogenic | Lynch syndrome 4 | 2022-04-14 | criteria provided, single submitter | clinical testing |