ClinVar Miner

Submissions for variant NM_203447.4(DOCK8):c.4109G>A (p.Arg1370His)

gnomAD frequency: 0.00002  dbSNP: rs753480025
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001042604 SCV001206298 uncertain significance Combined immunodeficiency due to DOCK8 deficiency 2022-06-13 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1370 of the DOCK8 protein (p.Arg1370His). This variant is present in population databases (rs753480025, gnomAD 0.005%). 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: 840574). 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. 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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV001195229 SCV001365536 uncertain significance not specified 2019-10-18 criteria provided, single submitter clinical testing The p.Arg1370His variant in DOCK8 has not been previously reported in individuals with hyper-IgE syndrome but has been identified in 7/282848 chromosomes by gnomAD (http://gnomad.broadinstitute.org). One mammal (bush baby) carries a histidine at this position despite high nearby amino acid conservation. In addition, computational prediction tools and conservation analyses suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. ACMG/AMP Criteria applied: PM2, BP4.
Ambry Genetics RCV004031292 SCV004859252 uncertain significance Inborn genetic diseases 2023-12-06 criteria provided, single submitter clinical testing The c.4109G>A (p.R1370H) alteration is located in exon 32 (coding exon 32) of the DOCK8 gene. This alteration results from a G to A substitution at nucleotide position 4109, causing the arginine (R) at amino acid position 1370 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Breakthrough Genomics, Breakthrough Genomics RCV004693490 SCV005196257 uncertain significance not provided criteria provided, single submitter not provided

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