Submissions for variant NM_002878.4(RAD51D):c.26G>T (p.Cys9Phe)

dbSNP: rs140825795

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000524888	SCV000651727	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 4	2025-01-14	criteria provided, single submitter	clinical testing	This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 9 of the RAD51D protein (p.Cys9Phe). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with RAD51D-related conditions. ClinVar contains an entry for this variant (Variation ID: 472595). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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	RCV000567220	SCV000667142	uncertain significance	Hereditary cancer-predisposing syndrome	2023-05-05	criteria provided, single submitter	clinical testing	The p.C9F variant (also known as c.26G>T), located in coding exon 1 of the RAD51D gene, results from a G to T substitution at nucleotide position 26. The cysteine at codon 9 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health	RCV000567220	SCV000912986	uncertain significance	Hereditary cancer-predisposing syndrome	2019-04-03	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000524888	SCV005054019	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 4	2024-01-24	criteria provided, single submitter	clinical testing
GeneDx	RCV004592600	SCV005078136	uncertain significance	not provided	2023-12-28	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified in an individual undergoing hereditary cancer genetic counseling (PMID: 36977404); This variant is associated with the following publications: (PMID: 21822264, 36977404, 21111057, 36243179)