Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001235169 | SCV001407843 | uncertain significance | Severe combined immunodeficiency due to DNA-PKcs deficiency | 2019-07-30 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with aspartic acid at codon 4000 of the PRKDC protein (p.Asn4000Asp). The asparagine residue is weakly conserved and there is a small physicochemical difference between asparagine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PRKDC-related conditions. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 | RCV004033272 | SCV002644253 | uncertain significance | not specified | 2022-01-15 | criteria provided, single submitter | clinical testing | The p.N4000D variant (also known as c.11998A>G), located in coding exon 84 of the PRKDC gene, results from an A to G substitution at nucleotide position 11998. The asparagine at codon 4000 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is conserved. 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. |