ClinVar Miner

Submissions for variant NM_203447.3(DOCK8):c.2275G>A (p.Val759Met) (rs148693111)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000317094 SCV000480147 uncertain significance Hyper-IgE syndrome 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000697622 SCV000826243 uncertain significance Hyperimmunoglobulin E recurrent infection syndrome, autosomal recessive 2018-12-22 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 759 of the DOCK8 protein (p.Val759Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs148693111, ExAC 0.04%). This variant has been observed in the heterozygous state in several individuals with common variable immunodeficiency, however other variants in primary immunodeficiency genes were also identified (PMID: 29867916). ClinVar contains an entry for this variant (Variation ID: 366864). 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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