ClinVar Miner

Submissions for variant NM_203447.4(DOCK8):c.3988C>G (p.Leu1330Val)

gnomAD frequency: 0.00076  dbSNP: rs148081681
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000439452 SCV000512850 uncertain significance not provided 2017-01-06 criteria provided, single submitter clinical testing The L1330V variant in the DOCK8 gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. However, the variant has been observed in the homozygous state in one unaffected individual at GeneDx. The NHLBI Exome Sequencing Project reports L1330V was observed in 10/4406 (0.23%) alleles from individuals of African-American background, and the 1000 Genomes Project Consortium reports it was observed in 2/1322 (0.15%) alleles from individuals of African background, indicating it may be a rare variant in these populations. The L1330V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV003595959 SCV001060712 benign Autosomal recessive hyper-IgE syndrome 2024-01-04 criteria provided, single submitter clinical testing
Baylor Genetics RCV001087724 SCV001527706 uncertain significance Combined immunodeficiency due to DOCK8 deficiency 2018-03-23 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
PreventionGenetics, part of Exact Sciences RCV003912613 SCV004737371 likely benign DOCK8-related disorder 2024-02-10 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 RCV001251750 SCV001427491 uncertain significance Intellectual disability 2019-01-01 no assertion criteria provided clinical testing

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