ClinVar Miner

Submissions for variant NM_005431.2(XRCC2):c.620A>G (p.Glu207Gly) (rs61762969)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115894 SCV000149803 likely benign not specified 2017-09-21 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
CSER _CC_NCGL, University of Washington RCV000211556 SCV000212185 uncertain significance Malignant tumor of colon 2015-03-11 criteria provided, single submitter research
Invitae RCV000791413 SCV000550370 uncertain significance not provided 2019-10-29 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glycine at codon 207 of the XRCC2 protein (p.Glu207Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is present in population databases (rs61762969, ExAC 0.02%). This variant has been reported in the literature in individuals affected with breast and pancreatic cancer, and an unaffected control individual (PMID: 23054243, 28767289). ClinVar contains an entry for this variant (Variation ID: 127960). Experimental studies have shown that this missense change does not impact XRCC2 DNA repair activity (PMID: 27233470). 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.
Ambry Genetics RCV000571792 SCV000675840 uncertain significance Hereditary cancer-predisposing syndrome 2020-05-07 criteria provided, single submitter clinical testing The p.E207G variant (also known as c.620A>G), located in coding exon 3 of the XRCC2 gene, results from an A to G substitution at nucleotide position 620. The glutamic acid at codon 207 is replaced by glycine, an amino acid with similar properties. This variant was identified in 1/3548 familial breast cancer cases (0.03%) and 1/1435 healthy controls (0.07%) in an international study (Hilbers FS et al. J. Med. Genet. 2012 Oct;49:618-20). Another study found that this variant allowed XRCC2 to retain 91% of wildtype function (Hilbers FS et al. Hum. Mutat. 2016 Sep;37:914-25). This variant, called a variant of uncertain significance by the study authors, has also been reported in an individual with pancreatic ductal adenocarcinoma (Shindo K et al. J. Clin. Oncol., 2017 Oct;35:3382-3390). This amino acid position is 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.
Mendelics RCV000709052 SCV000838286 uncertain significance Hereditary Cancer Syndrome 2018-07-02 criteria provided, single submitter clinical testing
Mendelics RCV000988014 SCV001137561 uncertain significance Fanconi anemia, complementation group U 2019-05-28 criteria provided, single submitter clinical testing
Leiden Open Variation Database RCV000791413 SCV001364735 uncertain significance not provided 2016-04-14 no assertion criteria provided curation Curator: Arleen D. Auerbach. Submitter to LOVD: Florentine Hilbers.

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