ClinVar Miner

Submissions for variant NM_203447.4(DOCK8):c.180G>T (p.Glu60Asp)

gnomAD frequency: 0.00021  dbSNP: rs370107163
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003596559 SCV000931165 uncertain significance Autosomal recessive hyper-IgE syndrome 2022-03-27 criteria provided, single submitter clinical testing 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 missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 639165). This variant has not been reported in the literature in individuals affected with DOCK8-related conditions. This variant is present in population databases (rs370107163, gnomAD 0.04%). This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 60 of the DOCK8 protein (p.Glu60Asp).
Genetic Services Laboratory, University of Chicago RCV001816840 SCV002070361 uncertain significance not specified 2020-12-31 criteria provided, single submitter clinical testing DNA sequence analysis of the DOCK8 gene demonstrated a sequence change, c.180G>T, in exon 3 that results in an amino acid change, p.Glu60Asp. This sequence change does not appear to have been previously described in patients with DOCK8-related disorders and has been described in the gnomAD database with a low population frequency of 0.048% in African subpopulations (dbSNP rs370107163). The p.Glu60Asp change affects a poorly conserved amino acid residue located in a domain of the DOCK8 protein that is not known to be functional. The p.Glu60Asp substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Glu60Asp change remains unknown at this time.
Ambry Genetics RCV004027399 SCV004859240 uncertain significance Inborn genetic diseases 2022-08-30 criteria provided, single submitter clinical testing The c.180G>T (p.E60D) alteration is located in exon 3 (coding exon 3) of the DOCK8 gene. This alteration results from a G to T substitution at nucleotide position 180, causing the glutamic acid (E) at amino acid position 60 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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