Submissions for variant NM_058216.3(RAD51C):c.317C>T (p.Ala106Val)

dbSNP: rs1060502594

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000461172	SCV000550212	uncertain significance	Fanconi anemia complementation group O	2022-02-09	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 106 of the RAD51C protein (p.Ala106Val). ClinVar contains an entry for this variant (Variation ID: 409852). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RAD51C protein function.
Ambry Genetics	RCV000561186	SCV000667121	uncertain significance	Hereditary cancer-predisposing syndrome	2022-11-23	criteria provided, single submitter	clinical testing	The p.A106V variant (also known as c.317C>T), located in coding exon 2 of the RAD51C gene, results from a C to T substitution at nucleotide position 317. The alanine at codon 106 is replaced by valine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 175000 alleles tested) in our clinical cohort. 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.
Counsyl	RCV000662698	SCV000785435	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 3; Fanconi anemia complementation group O	2017-08-08	criteria provided, single submitter	clinical testing
GeneDx	RCV001584160	SCV001810648	uncertain significance	not provided	2019-04-16	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge
Color Diagnostics, LLC DBA Color Health	RCV000561186	SCV002052706	uncertain significance	Hereditary cancer-predisposing syndrome	2021-07-14	criteria provided, single submitter	clinical testing	This missense variant replaces alanine with valine at codon 106 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.
Myriad Genetics, Inc.	RCV003316569	SCV004019960	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.