ClinVar Miner

Submissions for variant NM_203447.4(DOCK8):c.380G>A (p.Arg127His)

gnomAD frequency: 0.00196  dbSNP: rs150742426
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000645163 SCV000479543 likely benign Combined immunodeficiency due to DOCK8 deficiency 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx RCV001531727 SCV000730738 likely benign not provided 2018-12-11 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 32084423)
Invitae RCV003761945 SCV000766905 benign Autosomal recessive hyper-IgE syndrome 2024-01-24 criteria provided, single submitter clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000645163 SCV001468372 uncertain significance Combined immunodeficiency due to DOCK8 deficiency 2021-03-30 criteria provided, single submitter clinical testing DOCK8 NM_203447.3 exon 4 p.Arg127His (c.380G>A): This variant has been reported in the literature as a compound heterozygote in 1 individual with inflammatory bowel disease (IBD) (Crowley 2020 PMID:32084423). This variant is present in 0.3% (464/129078) of European alleles, including 2 homozygotes in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/9-289557-G-A?dataset=gnomad_r2_1). This variant is present in ClinVar, with several labs classifying this variant as Benign or Likely Benign (Variation ID:366538). Evolutionary conservation suggests that this variant may impact the protein; computational predictive tools for this variant are unclear. In summary, data on this variant suggests that this variant does not cause disease, but requires further evidence. Therefore, the clinical significance of this variant is uncertain.
CeGaT Center for Human Genetics Tuebingen RCV001531727 SCV001746985 likely benign not provided 2024-04-01 criteria provided, single submitter clinical testing DOCK8: BP4, BS2
Genetic Services Laboratory, University of Chicago RCV001821120 SCV002066416 likely benign not specified 2021-11-30 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003922651 SCV004748786 likely benign DOCK8-related disorder 2020-06-03 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille RCV001251744 SCV001427485 likely benign Intellectual disability 2019-01-01 no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV001531727 SCV001931598 likely benign not provided no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV001531727 SCV001963278 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001531727 SCV001971881 likely benign not provided no assertion criteria provided clinical testing

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