Submissions for variant NM_002878.4(RAD51D):c.16G>C (p.Val6Leu)

dbSNP: rs368198698

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001192468	SCV001360605	uncertain significance	not specified	2019-10-04	criteria provided, single submitter	clinical testing	Variant summary: RAD51D c.16G>C (p.Val6Leu) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 247238 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.16G>C in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001859166	SCV002301123	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 4	2022-10-02	criteria provided, single submitter	clinical testing	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. 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. ClinVar contains an entry for this variant (Variation ID: 928509). This variant has not been reported in the literature in individuals affected with RAD51D-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 6 of the RAD51D protein (p.Val6Leu).
Ambry Genetics	RCV002402558	SCV002714274	uncertain significance	Hereditary cancer-predisposing syndrome	2023-09-24	criteria provided, single submitter	clinical testing	The p.V6L variant (also known as c.16G>C), located in coding exon 1 of the RAD51D gene, results from a G to C substitution at nucleotide position 16. The valine at codon 6 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is poorly 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.