Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001238627 | SCV001411451 | uncertain significance | Severe combined immunodeficiency due to DNA-PKcs deficiency | 2020-01-10 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with glutamine at codon 3247 of the PRKDC protein (p.Arg3247Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Not Available; Align-GVGD: Class C0). 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 | RCV002379909 | SCV002695385 | uncertain significance | Inborn genetic diseases | 2021-11-06 | criteria provided, single submitter | clinical testing | The p.R3247Q variant (also known as c.9740G>A), located in coding exon 69 of the PRKDC gene, results from a G to A substitution at nucleotide position 9740. The arginine at codon 3247 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |