ClinVar Miner

Submissions for variant NM_005431.2(XRCC2):c.608C>T (p.Ser203Leu)

gnomAD frequency: 0.00003  dbSNP: rs143856570
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000229655 SCV000288892 uncertain significance not provided 2024-01-11 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 203 of the XRCC2 protein (p.Ser203Leu). This variant is present in population databases (rs143856570, gnomAD 0.006%). 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: 240162). 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 with a negative predictive value of 80%. 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 RCV001024881 SCV000838288 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-02 criteria provided, single submitter clinical testing
Mendelics RCV000988016 SCV001137563 uncertain significance Fanconi anemia complementation group U 2019-05-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV001024881 SCV001186972 uncertain significance Hereditary cancer-predisposing syndrome 2021-07-08 criteria provided, single submitter clinical testing The p.S203L variant (also known as c.608C>T), located in coding exon 3 of the XRCC2 gene, results from a C to T substitution at nucleotide position 608. The serine at codon 203 is replaced by leucine, an amino acid with dissimilar 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000229655 SCV004221591 uncertain significance not provided 2022-12-28 criteria provided, single submitter clinical testing The frequency of this variant in the general population, 0.000016 (4/251386 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in individuals with breast cancer in a breast cancer association study (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/XRCC2)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.

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