Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000160951 | SCV000211658 | uncertain significance | not provided | 2022-07-20 | criteria provided, single submitter | clinical testing | Not observed 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, 19327148) |
| Labcorp Genetics |
RCV000475132 | SCV000551322 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 4 | 2024-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 249 of the RAD51D protein (p.Asn249Asp). This variant is present in population databases (rs730881949, gnomAD 0.002%). This missense change has been observed in individual(s) with ovarian cancer (PMID: 34326862). ClinVar contains an entry for this variant (Variation ID: 182862). 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. |
| Ambry Genetics | RCV000562724 | SCV000663832 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-10-26 | criteria provided, single submitter | clinical testing | The p.N249D variant (also known as c.745A>G), located in coding exon 9 of the RAD51D gene, results from an A to G substitution at nucleotide position 745. The asparagine at codon 249 is replaced by aspartic acid, an amino acid with highly similar properties. This variant was identified in a patient with breast cancer as part of a large Canadian cohort study of 2870 individuals (Bhai P et al. Front Genet, 2021 Jul;12:698595). This amino acid position is highly 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. |
| Color Diagnostics, |
RCV000562724 | SCV000691362 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-04 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with aspartic acid at codon 249 of the RAD51D protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RAD51D-related disorders in the literature. This variant has been identified in 2/250988 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. |
| Baylor Genetics | RCV000475132 | SCV005054013 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 4 | 2024-02-06 | criteria provided, single submitter | clinical testing |