Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000480126 | SCV000572088 | uncertain significance | not provided | 2016-11-01 | criteria provided, single submitter | clinical testing | The Y1086H variant in the PRKDC gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The Y1086H variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).. The Y1086H variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret Y1086H as a variant of uncertain significance. |
| Labcorp Genetics |
RCV001851238 | SCV002292510 | uncertain significance | Severe combined immunodeficiency due to DNA-PKcs deficiency | 2021-04-29 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 422582). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. This sequence change replaces tyrosine with histidine at codon 1086 of the PRKDC protein (p.Tyr1086His). The tyrosine residue is highly conserved and there is a moderate physicochemical difference between tyrosine and histidine. |
| Ambry Genetics | RCV004659059 | SCV005151356 | uncertain significance | not specified | 2024-05-17 | criteria provided, single submitter | clinical testing | The p.Y1086H variant (also known as c.3256T>C), located in coding exon 27 of the PRKDC gene, results from a T to C substitution at nucleotide position 3256. The tyrosine at codon 1086 is replaced by histidine, an amino acid with similar properties. This amino acid position is conserved. 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. |