Submissions for variant NM_058216.3(RAD51C):c.4C>G (p.Arg2Gly)

dbSNP: rs758029117

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000663126	SCV000786260	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 3; Fanconi anemia complementation group O	2018-03-30	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000772906	SCV000906288	uncertain significance	Hereditary cancer-predisposing syndrome	2022-09-06	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with glycine at codon 2 of the RAD51C protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with familial breast cancer (PMID: 21597919). This variant has been identified in 1/251270 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000986010	SCV001134787	uncertain significance	not provided	2018-10-11	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001861727	SCV002309407	uncertain significance	Fanconi anemia complementation group O	2024-01-30	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 2 of the RAD51C protein (p.Arg2Gly). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with breast cancer (PMID: 21597919). ClinVar contains an entry for this variant (Variation ID: 548876). 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.
Ambry Genetics	RCV000772906	SCV002641777	benign	Hereditary cancer-predisposing syndrome	2024-05-16	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Myriad Genetics, Inc.	RCV003316791	SCV004019975	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 3	2023-04-05	criteria provided, single submitter	clinical testing	This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
Leiden Open Variation Database	RCV000986010	SCV001365237	uncertain significance	not provided	2014-11-02	no assertion criteria provided	curation	Curator: Arleen D. Auerbach. Submitter to LOVD: Johan den Dunnen.