Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000572946 | SCV000670787 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-06-18 | criteria provided, single submitter | clinical testing | The p.P726S variant (also known as c.2176C>T), located in coding exon 13 of the PMS2 gene, results from a C to T substitution at nucleotide position 2176. The proline at codon 726 is replaced by serine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV002526884 | SCV002965072 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2022-05-24 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 484274). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 726 of the PMS2 protein (p.Pro726Ser). 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. |