Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Mendelics | RCV000988134 | SCV001137733 | uncertain significance | Combined immunodeficiency due to DOCK8 deficiency | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV003595649 | SCV001399411 | uncertain significance | Autosomal recessive hyper-IgE syndrome | 2020-11-11 | criteria provided, single submitter | clinical testing | 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 disruptive, 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. 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. This variant has not been reported in the literature in individuals with DOCK8-related conditions. This variant is present in population databases (rs766901544, ExAC 0.06%). This sequence change replaces asparagine with serine at codon 622 of the DOCK8 protein (p.Asn622Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. |