ClinVar Miner

Submissions for variant NM_203447.3(DOCK8):c.1623C>G (p.His541Gln) (rs200201944)

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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 RCV000275558 SCV000479728 uncertain significance Hyper-IgE syndrome 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000822154 SCV000962944 uncertain significance Hyperimmunoglobulin E recurrent infection syndrome, autosomal recessive 2018-12-04 criteria provided, single submitter clinical testing This sequence change replaces histidine with glutamine at codon 541 of the DOCK8 protein (p.His541Gln). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and glutamine. This variant is present in population databases (rs200201944, ExAC 0.09%). This variant has not been reported in the literature in individuals with DOCK8-related disease. ClinVar contains an entry for this variant (Variation ID: 366676). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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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