Submissions for variant NM_002878.4(RAD51D):c.883C>G (p.Leu295Val)

dbSNP: rs752910287

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000476276	SCV000551362	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 4	2024-12-31	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 295 of the RAD51D protein (p.Leu295Val). This variant is present in population databases (rs752910287, gnomAD no frequency). 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: 410562). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt RAD51D protein function with a negative predictive value of 80%. 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.
GeneDx	RCV000484734	SCV000567475	uncertain significance	not provided	2023-07-21	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 21111057, 19327148, 14704354)
Ambry Genetics	RCV000561823	SCV000663815	uncertain significance	Hereditary cancer-predisposing syndrome	2023-10-17	criteria provided, single submitter	clinical testing	The p.L295V variant (also known as c.883C>G), located in coding exon 9 of the RAD51D gene, results from a C to G substitution at nucleotide position 883. The leucine at codon 295 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly 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.
Color Diagnostics, LLC DBA Color Health	RCV000561823	SCV000904084	uncertain significance	Hereditary cancer-predisposing syndrome	2022-07-25	criteria provided, single submitter	clinical testing	This missense variant replaces leucine with valine at codon 295 of the RAD51D 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 been identified in 1/251420 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.
Mendelics	RCV002248687	SCV002519251	uncertain significance	not specified	2022-05-04	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000561823	SCV002534866	uncertain significance	Hereditary cancer-predisposing syndrome	2022-03-06	criteria provided, single submitter	curation
Baylor Genetics	RCV000476276	SCV005053996	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 4	2024-03-16	criteria provided, single submitter	clinical testing