Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001011456 | SCV001171778 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-07-07 | criteria provided, single submitter | clinical testing | The p.D472G variant (also known as c.1415A>G), located in coding exon 9 of the RAD50 gene, results from an A to G substitution at nucleotide position 1415. The aspartic acid at codon 472 is replaced by glycine, an amino acid with similar properties. This amino acid position is highly conserved through mammals but not in all 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. |
Invitae | RCV001011456 | SCV001511201 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-27 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 819156). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 472 of the RAD50 protein (p.Asp472Gly). |