Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000165135 | SCV000215845 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-14 | criteria provided, single submitter | clinical testing | The p.K48R variant (also known as c.143A>G), located in coding exon 2 of the RAD51D gene, results from an A to G substitution at nucleotide position 143. The lysine at codon 48 is replaced by arginine, an amino acid with highly similar properties. 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. |
Labcorp Genetics |
RCV001322760 | SCV001513647 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 4 | 2022-05-31 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 48 of the RAD51D protein (p.Lys48Arg). 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. Studies have shown that this missense change is associated with altered splicing resulting in unknown protein product impact (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 185676). This variant has not been reported in the literature in individuals affected with RAD51D-related conditions. This variant is not present in population databases (gnomAD no frequency). |