Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Fulgent Genetics, |
RCV001062797 | SCV005641833 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 4 | 2024-03-01 | criteria provided, single submitter | clinical testing | |
| MGZ Medical Genetics Center | RCV001062797 | SCV002580359 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 4 | 2021-09-14 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000708748 | SCV001355213 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-15 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with glutamic acid at codon 90 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 reported for this variant. This variant has been reported in an individual affected with breast cancer who also carried a pathogenic co-variant in the ATM gene (PMID: 35127508). Another study detected this variant 3 times in a cohort of individuals referred for genetic testing (PMID: 31159747). 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. |
| Labcorp Genetics |
RCV001062797 | SCV001227620 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 4 | 2024-08-07 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 90 of the RAD51D protein (p.Asp90Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with RAD51D-related conditions (PMID: 31159747). ClinVar contains an entry for this variant (Variation ID: 584559). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae 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 | RCV000708748 | SCV001177184 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-12-16 | criteria provided, single submitter | clinical testing | The p.D90E variant (also known as c.270T>A), located in coding exon 4 of the RAD51D gene, results from a T to A substitution at nucleotide position 270. The aspartic acid at codon 90 is replaced by glutamic acid, 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 deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Gene |
RCV000708748 | SCV000822176 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-08-01 | criteria provided, single submitter | clinical testing |