Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000198235 | SCV000253846 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-02-20 | 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: 216075). 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.Ser547Argfs*14) 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). |
| Gene |
RCV000479164 | SCV000570067 | pathogenic | not provided | 2016-04-21 | criteria provided, single submitter | clinical testing | This deletion of 2 nucleotides in PMS2 is denoted c.1638_1639delTT at the cDNA level and p.Ser547ArgfsX14 (S547RfsX14) at the protein level. The normal sequence, with the bases that are deleted in braces, is CTTT[TT]CAGA. The deletion causes a frameshift which changes a Serine to an Arginine at codon 547, and creates a premature stop codon at position 14 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic. |
| Ambry Genetics | RCV002390532 | SCV002703029 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-01-04 | criteria provided, single submitter | clinical testing | The c.1638_1639delTT pathogenic mutation, located in coding exon 11 of the PMS2 gene, results from a deletion of two nucleotides at nucleotide positions 1638 to 1639, causing a translational frameshift with a predicted alternate stop codon (p.S547Rfs*14). 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, |
RCV003454501 | SCV004187777 | pathogenic | Lynch syndrome 4 | 2023-09-20 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
| Baylor Genetics | RCV003454501 | SCV004203422 | likely pathogenic | Lynch syndrome 4 | 2021-06-04 | criteria provided, single submitter | clinical testing |