Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000235653 | SCV000293499 | uncertain significance | not provided | 2015-11-16 | criteria provided, single submitter | clinical testing | This variant is denoted XRCC2 c.644G>A at the cDNA level, p.Arg215Gln (R215Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGA>CAA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. XRCC2 Arg215Gln 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 Arginine and Glutamine differ in some properties, this is considered a semi-conservative amino acid substitution. XRCC2 Arg215Gln occurs at a position that is not conserved and is located in the ATPase domain (Kim 2011). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether XRCC2 Arg215Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
Ambry Genetics | RCV000564280 | SCV000675850 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-11 | criteria provided, single submitter | clinical testing | The p.R215Q variant (also known as c.644G>A), located in coding exon 3 of the XRCC2 gene, results from a G to A substitution at nucleotide position 644. The arginine at codon 215 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Mendelics | RCV000988013 | SCV001137559 | uncertain significance | Fanconi anemia complementation group U | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000235653 | SCV003299963 | uncertain significance | not provided | 2024-01-12 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 215 of the XRCC2 protein (p.Arg215Gln). This variant is present in population databases (rs762828701, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with XRCC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 246108). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |