ClinVar Miner

Submissions for variant NM_203447.3(DOCK8):c.3614C>G (p.Pro1205Arg) (rs1310119190)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522427 SCV000617981 uncertain significance not provided 2017-07-07 criteria provided, single submitter clinical testing The P1205R variant in the DOCK8 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The P1205R variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P1205R 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 not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret P1205R as a variant of uncertain significance.
Invitae RCV000702101 SCV000830936 uncertain significance Hyperimmunoglobulin E recurrent infection syndrome, autosomal recessive 2018-05-18 criteria provided, single submitter clinical testing This sequence change replaces proline with arginine at codon 1205 of the DOCK8 protein (p.Pro1205Arg). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DOCK8-related disease. ClinVar contains an entry for this variant (Variation ID: 449656). 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.

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