ClinVar Miner

Submissions for variant NM_004946.3(DOCK2):c.3310C>T (p.Arg1104Trp) (rs780318765)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000180782 SCV000960431 uncertain significance Immunodeficiency 40 2018-09-12 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 1104 of the DOCK2 protein (p.Arg1104Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs780318765, ExAC 0.001%). This variant has been observed in individuals affected with combined immunodeficiency (PMID: 26083206, 29204803). ClinVar contains an entry for this variant (Variation ID: 199260). Experimental studies have shown that patient-derived cells that carry both the p.Arg1104Trp variant and a truncating variant (p.Gln1324*) demonstrate impaired T cell and NK cell function as well as impaired virally-stimulated IFN production (PMID: 26083206). Most assays described in this study did not assess the effect of the p.Arg1104Trp variant alone. Cells derived from the proband's parent (heterozygous carrier of only the p.Arg1104Trp variant) demonstrated impaired virally-stimulated IFN production similar to what was seen in the proband, however, this parent is clinically unaffected.  Furthermore, cells from this same unaffected parent demonstrate T-cell RAC activation similar to that seen in healthy control cells. Therefore, the clinical significance of these findings is unclear at this time. 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.
OMIM RCV000180782 SCV000233270 pathogenic Immunodeficiency 40 2015-06-18 no assertion criteria provided literature only

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