Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV004333511 | SCV003998160 | uncertain significance | not specified | 2023-05-23 | criteria provided, single submitter | clinical testing | The p.D382A variant (also known as c.1145A>C), located in coding exon 12 of the PRKDC gene, results from an A to C substitution at nucleotide position 1145. The aspartic acid at codon 382 is replaced by alanine, an amino acid with dissimilar properties. This amino acid position is conserved. 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 |
RCV003586404 | SCV004310391 | uncertain significance | Severe combined immunodeficiency due to DNA-PKcs deficiency | 2023-07-25 | 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. 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 PRKDC protein function. ClinVar contains an entry for this variant (Variation ID: 2564560). This variant has not been reported in the literature in individuals affected with PRKDC-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 alanine, which is neutral and non-polar, at codon 382 of the PRKDC protein (p.Asp382Ala). |