Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000793507 | SCV000932862 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2022-02-17 | criteria provided, single submitter | clinical testing | 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. This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 271 of the PMS2 protein (p.Gly271Asp). This variant is not present in population databases (gnomAD no frequency). 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: 640477). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. |
| Ambry Genetics | RCV002422685 | SCV002678793 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-09-13 | criteria provided, single submitter | clinical testing | The p.G271D variant (also known as c.812G>A), located in coding exon 8 of the PMS2 gene, results from a G to A substitution at nucleotide position 812. The glycine at codon 271 is replaced by aspartic acid, an amino acid with similar properties. This variant has been identified in probands whose Lynch syndrome-associated tumor demonstrated high microsatellite instability and/or loss of PMS2 expression by immunohistochemistry (Ambry internal data). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |