Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000161109 | SCV000211844 | uncertain significance | not specified | 2017-03-21 | criteria provided, single submitter | clinical testing | This variant is denoted XRCC2 c.613T>G at the cDNA level, p.Ser205Ala (S205A) at the protein level, and results in the change of a Serine to an Alanine (TCA>GCA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. XRCC2 Ser205Ala was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. Since Serine and Alanine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. XRCC2 Ser205Ala 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 Ser205Ala is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
Eurofins Ntd Llc |
RCV000726016 | SCV000341255 | uncertain significance | not provided | 2016-04-29 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV001024935 | SCV000838287 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000726016 | SCV000942467 | uncertain significance | not provided | 2023-10-19 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 205 of the XRCC2 protein (p.Ser205Ala). This variant is present in population databases (rs56103026, gnomAD 0.05%). 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: 182997). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt XRCC2 protein function. 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. |
Mendelics | RCV000988015 | SCV001137562 | uncertain significance | Fanconi anemia complementation group U | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV001024935 | SCV001187033 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-15 | criteria provided, single submitter | clinical testing | The p.S205A variant (also known as c.613T>G), located in coding exon 3 of the XRCC2 gene, results from a T to G substitution at nucleotide position 613. The serine at codon 205 is replaced by alanine, an amino acid with similar properties. This alteration has been reported in a cohort of African-American women with breast cancer (Ding YC et al. Fam Cancer, 2018 04;17:187-195). This amino acid position is not well 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000726016 | SCV004221592 | likely benign | not provided | 2022-10-09 | criteria provided, single submitter | clinical testing |