Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001013479 | SCV001174071 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-01-01 | criteria provided, single submitter | clinical testing | The p.A63T variant (also known as c.187G>A), located in coding exon 3 of the RAD51D gene, results from a G to A substitution at nucleotide position 187. The alanine at codon 63 is replaced by threonine, an amino acid with similar properties. This amino acid position is well 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. |
| Labcorp Genetics |
RCV001037370 | SCV001200780 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 4 | 2024-12-12 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 63 of the RAD51D protein (p.Ala63Thr). This variant is present in population databases (rs777402267, gnomAD 0.003%). 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: 820232). 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%. Studies have shown that this missense change is associated with altered splicing (PMID: 34200360). 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003478619 | SCV004220163 | uncertain significance | not provided | 2023-06-16 | criteria provided, single submitter | clinical testing | This variant has not been reported in individuals with RAD51D -related conditions in the published literature. The frequency of this variant in the general population, 0.000004 (1/251408 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 conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Color Diagnostics, |
RCV001013479 | SCV004357178 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-30 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with threonine at codon 63 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 been reported to have been detected in a breast cancer case-control meta-analysis but the cancer status of the carrier was not provided (PMID: 34200360). This variant has been identified in 1/251408 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. |