Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000760335 | SCV000890194 | pathogenic | not provided | 2018-05-18 | criteria provided, single submitter | clinical testing | This variant is denoted PMS2 c.730C>T at the cDNA level and p.Gln244Ter (Q244X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), 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 as a germline variant, it is considered pathogenic. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000760335 | SCV001134613 | pathogenic | not provided | 2019-04-02 | criteria provided, single submitter | clinical testing | The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and not found in general population data. |
Ambry Genetics | RCV001026254 | SCV001188598 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-06-10 | criteria provided, single submitter | clinical testing | The p.Q244* pathogenic mutation (also known as c.730C>T), located in coding exon 7 of the PMS2 gene, results from a C to T substitution at nucleotide position 730. This changes the amino acid from a glutamine to a stop codon within coding exon 7. This mutation was observed in a patient with metastatic prostate cancer (Mijuskovic M et al. Br. J. Cancer 2018 Jul;119(1):96-104). 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. |
Invitae | RCV001221708 | SCV001393768 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-12-29 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln244*) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with prostate cancer (PMID: 29915322). ClinVar contains an entry for this variant (Variation ID: 620098). For these reasons, this variant has been classified as Pathogenic. |
Myriad Genetics, |
RCV003453566 | SCV004187711 | 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. |
Color Diagnostics, |
RCV001026254 | SCV004359664 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-09-06 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 7 of the PMS2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in an individual affected with metastatic prostate cancer (PMID: 29915322). 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. |