ClinVar Miner

Submissions for variant NM_203447.4(DOCK8):c.1016C>T (p.Pro339Leu)

gnomAD frequency: 0.00008  dbSNP: rs145716710
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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 RCV000824280 SCV000965173 uncertain significance Combined immunodeficiency due to DOCK8 deficiency 2022-09-01 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 339 of the DOCK8 protein (p.Pro339Leu). This variant is present in population databases (rs145716710, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with DOCK8-related conditions. ClinVar contains an entry for this variant (Variation ID: 665900). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Genetic Services Laboratory, University of Chicago RCV001816912 SCV002065106 uncertain significance not specified 2021-05-19 criteria provided, single submitter clinical testing DNA sequence analysis of the DOCK8 gene demonstrated a sequence change, c.1016C>T, in exon 9 that results in an amino acid change, p.Pro339Leu. This sequence change has been described in the gnomAD database with a frequency of 0.02% in the European (non-Finnish) subpopulation (dbSNP rs145716710). The p.Pro339Leu change affects a highly conserved amino acid residue located in a domain of the DOCK8 protein that is not known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Pro339Leu substitution. This sequence change does not appear to have been previously described in patients with DOCK8-related. Due to the lack of sufficient evidences, the clinical significance of the p.Pro339Leu change remains unknown at this time.
GeneDx RCV005054275 SCV005687928 uncertain significance not provided 2024-07-30 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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