ClinVar Miner

Submissions for variant NM_005431.2(XRCC2):c.613T>G (p.Ser205Ala) (rs56103026)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000726016 SCV000341255 uncertain significance not provided 2016-04-29 criteria provided, single submitter clinical testing
Mendelics RCV000709053 SCV000838287 uncertain significance Hereditary Cancer Syndrome 2018-07-02 criteria provided, single submitter clinical testing
Invitae RCV000726016 SCV000942467 uncertain significance not provided 2019-10-28 criteria provided, single submitter clinical testing This sequence change replaces serine with alanine at codon 205 of the XRCC2 protein (p.Ser205Ala). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and alanine. This variant is present in population databases (rs56103026, ExAC 0.03%). This variant has not been reported in the literature in individuals with XRCC2-related disease. ClinVar contains an entry for this variant (Variation ID: 182997). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 2019-10-31 criteria provided, single submitter clinical testing Insufficient evidence

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