ClinVar Miner

Submissions for variant NM_203447.3(DOCK8):c.3216C>G (p.Ile1072Met) (rs370250940)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000768200 SCV000898651 uncertain significance Hyperimmunoglobulin E recurrent infection syndrome, autosomal recessive 2018-09-28 criteria provided, single submitter clinical testing DOCK8 NM_203447.3 exon 26 p.Ile1072Met (c.3216C>G): This variant has not been reported in the literature but is present in 19/23984 African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs370250940). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Invitae RCV000768200 SCV000965078 uncertain significance Hyperimmunoglobulin E recurrent infection syndrome, autosomal recessive 2018-08-20 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with methionine at codon 1072 of the DOCK8 protein (p.Ile1072Met). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is present in population databases (rs370250940, ExAC 0.02%). This variant has not been reported in the literature in individuals with DOCK8-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly 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.

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