ClinVar Miner

Submissions for variant NM_203447.3(DOCK8):c.3361A>G (p.Thr1121Ala)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000812532 SCV000952849 uncertain significance Hyperimmunoglobulin E recurrent infection syndrome, autosomal recessive 2018-12-03 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 1121 of the DOCK8 protein (p.Thr1121Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs373466608, ExAC 0.02%). This variant has not been reported in the literature in individuals with DOCK8-related conditions. 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 alanine 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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