Submissions for variant NM_005431.2(XRCC2):c.7A>G (p.Ser3Gly)

gnomAD frequency: 0.00001  dbSNP: rs762701579

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000484929	SCV000566164	uncertain significance	not provided	2024-12-09	criteria provided, single submitter	clinical testing	Observed in an individual with personal or family history of breast and/or ovarian cancer (PMID: 31159747); In silico analysis indicates that this missense variant does not alter protein structure/function; Variants in candidate genes are classified as variants of uncertain significance in accordance with ACMG guidelines (PMID: 25741868); This variant is associated with the following publications: (PMID: 31159747)
GeneKor MSA	RCV000708766	SCV000822213	uncertain significance	Hereditary cancer-predisposing syndrome	2018-08-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000708766	SCV001189538	likely benign	Hereditary cancer-predisposing syndrome	2024-03-08	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000484929	SCV001207419	uncertain significance	not provided	2023-05-07	criteria provided, single submitter	clinical testing	Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. ClinVar contains an entry for this variant (Variation ID: 418820). This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 3 of the XRCC2 protein (p.Ser3Gly). This variant is present in population databases (rs762701579, gnomAD 0.003%). This missense change has been observed in individual(s) with clinical features of XRCC2-related conditions (PMID: 31159747).
PreventionGenetics, part of Exact Sciences	RCV003401515	SCV004121167	uncertain significance	XRCC2-related disorder	2022-12-22	criteria provided, single submitter	clinical testing	The XRCC2 c.7A>G variant is predicted to result in the amino acid substitution p.Ser3Gly. This variant was reported with uncertain significance in study of individuals with a personal or family history of breast and/or ovarian cancer (Supplemental Table S5, Tsaousis et al. 2019. PubMed ID: 31159747). This variant is reported in 0.0031% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/7-152373158-T-C) and is reported as uncertain in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/418820/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.