Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000076853 | SCV000108345 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
| Ambry Genetics | RCV000572699 | SCV000674247 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-09-29 | criteria provided, single submitter | clinical testing | The c.2361_2364delCTTC pathogenic mutation, located in coding exon 14 of the PMS2 gene, results from a deletion of 4 nucleotides at nucleotide positions 2361 to 2364, causing a translational frameshift with a predicted alternate stop codon (p.F788Cfs*2). This mutation was previously identified in trans with another PMS2 alteration in a patient who was diagnosed with a brain tumor and colon cancer at ages 14 and 18 (De Rosa M et al. Oncogene 2000 Mar;19(13):1719-23). 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 | RCV000629975 | SCV000750931 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2024-01-06 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Phe788Cysfs*2) 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). The frequency data for this variant in the population databases (gnomAD) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. This premature translational stop signal has been observed in individual(s) with clinical features of autosomal recessive constitutional mismatch repair deficiency syndrome (CMMR-D) (PMID: 10763829). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 91338). For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV000657184 | SCV000778906 | pathogenic | not provided | 2022-02-04 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; This variant is associated with the following publications: (PMID: 21376568, 20531397, 30787465, 10763829) |
| Myriad Genetics, |
RCV003452991 | SCV004187679 | pathogenic | Lynch syndrome 4 | 2023-09-22 | 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 | RCV003452991 | SCV004205480 | pathogenic | Lynch syndrome 4 | 2023-08-21 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000009817 | SCV000030038 | pathogenic | Mismatch repair cancer syndrome 4 | 2000-03-23 | no assertion criteria provided | literature only |