Submissions for variant NM_005431.2(XRCC2):c.808T>G (p.Phe270Val)

gnomAD frequency: 0.00205  dbSNP: rs145085742

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000115899	SCV000149808	likely benign	not specified	2017-12-19	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000858406	SCV000288895	benign	not provided	2025-01-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000565731	SCV000675836	likely benign	Hereditary cancer-predisposing syndrome	2018-04-24	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.
Mendelics	RCV000988009	SCV001137555	likely benign	Fanconi anemia complementation group U	2019-05-28	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000115899	SCV002066409	likely benign	not specified	2021-06-23	criteria provided, single submitter	clinical testing	DNA sequence analysis of the XRCC2 gene demonstrated a sequence change, c.808T>G, in exon 3 that results in an amino acid change, p.Phe270Val. This sequence change does not appear to have been previously described in patients with XRCC2-related disorders and has been described in the gnomAD database with a low population frequency of 0.70% in African subpopulation (dbSNP rs145085742). The p.Phe270Val change affects a highly conserved amino acid residue located in a domain of the XRCC2 protein that is not known to be functional. The p.Phe270Val substitution appears to be deleterious using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Phe270Val change remains unknown at this time.
Sema4, Sema4	RCV000565731	SCV002538384	likely benign	Hereditary cancer-predisposing syndrome	2021-08-30	criteria provided, single submitter	curation
Breakthrough Genomics, Breakthrough Genomics	RCV000858406	SCV005219894	likely benign	not provided		criteria provided, single submitter	not provided
Leiden Open Variation Database	RCV000858406	SCV001364743	uncertain significance	not provided	2012-05-02	no assertion criteria provided	curation	Curator: Arleen D. Auerbach. Submitter to LOVD: Johan den Dunnen.
PreventionGenetics, part of Exact Sciences	RCV003925117	SCV004754586	likely benign	XRCC2-related disorder	2020-09-28	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).