Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000466147 | SCV000551979 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2024-05-28 | criteria provided, single submitter | clinical testing | This sequence change disrupts the translational stop signal of the PMS2 mRNA. It is expected to extend the length of the PMS2 protein by 2 additional amino acid residues. 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 variant has not been reported in the literature in individuals affected with PMS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 411040). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV001016024 | SCV001176930 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-18 | criteria provided, single submitter | clinical testing | The c.2587T>G variant (also known as p.*863GEXT*2), located in coding exon 15 of the PMS2 gene, results from a T to G substitution at nucleotide position 2587. This alteration disrupts the stop codon of the PMS2 gene and is predicted to preserve the native sequence while resulting in the elongation of the protein by two amino acids. The exact functional effect of the additional amino acids is unknown. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV002481461 | SCV002792486 | uncertain significance | Lynch syndrome 4; Mismatch repair cancer syndrome 4 | 2022-03-01 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV001016024 | SCV004358945 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-05 | criteria provided, single submitter | clinical testing | This variant changes the translational stop signal of the PMS2 protein to Glycine. Translation read-through is expected to extend the length of the PMS2 protein by 1 additional amino acids. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/201158 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Department of Pathology and Laboratory Medicine, |
RCV005355861 | SCV005913324 | uncertain significance | Lynch syndrome | 2022-11-28 | criteria provided, single submitter | clinical testing |