Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001070971 | SCV001236251 | uncertain significance | Combined immunodeficiency due to DOCK8 deficiency | 2022-10-07 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1018 of the DOCK8 protein (p.Asp1018Asn). This variant is present in population databases (rs142910397, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with DOCK8-related conditions. ClinVar contains an entry for this variant (Variation ID: 863900). 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 not expected to disrupt DOCK8 protein function. 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 | RCV002555900 | SCV003744337 | uncertain significance | Inborn genetic diseases | 2021-12-03 | criteria provided, single submitter | clinical testing | The c.3052G>A (p.D1018N) alteration is located in exon 25 (coding exon 25) of the DOCK8 gene. This alteration results from a G to A substitution at nucleotide position 3052, causing the aspartic acid (D) at amino acid position 1018 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |