Submissions for variant NM_058216.3(RAD51C):c.293G>C (p.Gly98Ala)

dbSNP: rs1060502586

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000475142	SCV000550194	uncertain significance	Fanconi anemia complementation group O	2021-02-06	criteria provided, single submitter	clinical testing	In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a RAD51C-related disease. This sequence change replaces glycine with alanine at codon 98 of the RAD51C protein (p.Gly98Ala). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and alanine.
Ambry Genetics	RCV000574385	SCV000663786	uncertain significance	Hereditary cancer-predisposing syndrome	2019-05-16	criteria provided, single submitter	clinical testing	The p.G98A variant (also known as c.293G>C), located in coding exon 2 of the RAD51C gene, results from a G to C substitution at nucleotide position 293. The glycine at codon 98 is replaced by alanine, an amino acid with similar properties. This amino acid position is not 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.
GeneDx	RCV001770346	SCV001994362	uncertain significance	not provided	2019-08-13	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Baylor Genetics	RCV003463923	SCV004207915	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 3	2023-10-12	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000574385	SCV004357105	uncertain significance	Hereditary cancer-predisposing syndrome	2022-06-21	criteria provided, single submitter	clinical testing	This missense variant replaces glycine with alanine at codon 98 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 not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified 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.