ClinVar Miner

Submissions for variant NM_002878.4(RAD51D):c.550G>A (p.Glu184Lys)

gnomAD frequency: 0.00001  dbSNP: rs200009601
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000167033 SCV000217856 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-14 criteria provided, single submitter clinical testing The p.E184K variant (also known as c.550G>A), located in coding exon 6 of the RAD51D gene, results from a G to A substitution at nucleotide position 550. The glutamic acid at codon 184 is replaced by lysine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV002291584 SCV000602161 uncertain significance not provided 2024-01-31 criteria provided, single submitter clinical testing The RAD51D c.550G>A (p.Glu184Lys) variant has not been reported in individuals with RAD51D-related conditions in the published literature. The frequency of this variant in the general population, 0.00027 (5/18376 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV000538714 SCV000651757 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 4 2025-01-17 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 184 of the RAD51D protein (p.Glu184Lys). This variant is present in population databases (rs200009601, gnomAD 0.02%). 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: 187314). 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.
Color Diagnostics, LLC DBA Color Health RCV000167033 SCV000686467 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-03 criteria provided, single submitter clinical testing
GeneDx RCV002291584 SCV002584126 uncertain significance not provided 2022-10-12 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; Observed in individuals with breast cancer (Chen et al., 2020); This variant is associated with the following publications: (PMID: 32091409, 21111057, 14704354)
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV000538714 SCV004239134 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 4 2024-01-31 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 72 of the RAD51D protein (p.Glu72Lys). This variant is present in population databases (rs200009601, gnomAD 0.02%). This variant observed in individuals with breast cancer (Chen et al., 2020); This variant is associated with the following publications: (PMID: 32091409, 21111057, 14704354) . ClinVar contains an entry for this variant (Variation ID: 187314) classified as uncertain significant . This amino acid position is poorly conserved (PhyloP=2.7) .In addition, this alteration is predicted to be tolerated by in silico analysis. 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.
Baylor Genetics RCV000538714 SCV005054027 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 4 2024-01-03 criteria provided, single submitter clinical testing

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