Submissions for variant NM_002878.4(RAD51D):c.339A>C (p.Lys113Asn)

dbSNP: rs786202507

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000165351	SCV000216075	uncertain significance	Hereditary cancer-predisposing syndrome	2023-04-28	criteria provided, single submitter	clinical testing	The p.K113N variant (also known as c.339A>C), located in coding exon 4 of the RAD51D gene, results from an A to C substitution at nucleotide position 339. The lysine at codon 113 is replaced by asparagine, an amino acid with similar 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.
Counsyl	RCV000409073	SCV000489085	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 4	2016-08-15	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000409073	SCV000551355	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 4	2024-11-27	criteria provided, single submitter	clinical testing	This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 113 of the RAD51D protein (p.Lys113Asn). This variant is not present in population databases (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: 185853). 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 expected to disrupt RAD51D protein function with a positive 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.
Color Diagnostics, LLC DBA Color Health	RCV000165351	SCV000686445	uncertain significance	Hereditary cancer-predisposing syndrome	2020-11-11	criteria provided, single submitter	clinical testing	This missense variant replaces lysine with asparagine at codon 113 within the ATP-binding motif of the ATPase domain of the RAD51D protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been performed for this variant. However, other missense mutations affecting the same codon (p.Lys113Arg and p.Lys113Ala) have been shown to severely reduce repair activity in DNA repair assay in cultured mammalian cells (PMID: 16236763). 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.
GeneDx	RCV001582653	SCV001819635	uncertain significance	not provided	2023-08-08	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; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 21111057, 14704354)
Sema4, Sema4	RCV000165351	SCV002534796	uncertain significance	Hereditary cancer-predisposing syndrome	2021-09-18	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV000409073	SCV004017776	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 4	2023-04-06	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.
Baylor Genetics	RCV000409073	SCV004200344	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 4	2023-09-29	criteria provided, single submitter	clinical testing