Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000215377 | SCV000279950 | uncertain significance | not provided | 2016-03-02 | criteria provided, single submitter | clinical testing | This variant is denoted PMS2 c.221G>C at the cDNA level, p.Gly74Ala (G74A) at the protein level, and results in the change of a Glycine to an Alanine (GGG>GCG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. PMS2 Gly74Ala was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Glycine and Alanine share similar properties, this is considered a conservative amino acid substitution. PMS2 Gly74Ala occurs at a position that is conserved across species and is located in the ATPase domain (Fukui 2011). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether PMS2 Gly74Ala is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
Ambry Genetics | RCV001014834 | SCV001175596 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-30 | criteria provided, single submitter | clinical testing | The p.G74A variant (also known as c.221G>C), located in coding exon 3 of the PMS2 gene, results from a G to C substitution at nucleotide position 221. The glycine at codon 74 is replaced by alanine, 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. |