ClinVar Miner

Submissions for variant NM_203447.3(DOCK8):c.4346C>T (p.Ser1449Leu) (rs370123223)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000419242 SCV000528262 likely benign not specified 2016-09-02 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000691493 SCV000819276 uncertain significance Hyperimmunoglobulin E recurrent infection syndrome, autosomal recessive 2018-10-29 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 1449 of the DOCK8 protein (p.Ser1449Leu). The serine residue is moderately conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs370123223, ExAC 0.03%). This variant has been observed in the homozygous state a family affected with DOCK8 deficiency, however the affected individuals in that family were also homozygous for a splice site variant (PMID: 27890707). ClinVar contains an entry for this variant (Variation ID: 386550). 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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