ClinVar Miner

Submissions for variant NM_203447.4(DOCK8):c.2017A>T (p.Ile673Phe)

dbSNP: rs372858877
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000213603 SCV000271698 uncertain significance not specified 2015-08-06 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Ile673Phe var iant in DOCK8 has not been previously reported in individuals with pulmonary dis ease, but has been identified in 20/66678 European chromosomes by the Exome Aggr egation Consortium (ExAC,; dbSNP rs372858877). Co mputational prediction tools and conservation analysis suggest that the p.Ile673 Phe variant may not impact the protein, though this information is not predictiv e enough to rule out pathogenicity. In summary, while the clinical significance of the p.Ile673Phe variant is uncertain, these data suggest that it is more like ly to be benign.
GeneDx RCV000766471 SCV000518140 uncertain significance not provided 2016-12-23 criteria provided, single submitter clinical testing The I605F variant in the DOCK8 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The I605F variant was not observed at any significant frequency in approximately 6,500 individuals of European and African American ancestry by the NHLBI Exome Sequencing Project. The I605F variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Isoleucine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret I605F as a variant of uncertain significance.
Invitae RCV003595894 SCV000949079 uncertain significance Autosomal recessive hyper-IgE syndrome 2024-01-29 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 673 of the DOCK8 protein (p.Ile673Phe). This variant is present in population databases (rs372858877, gnomAD 0.03%). 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: 228615). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt DOCK8 protein function with a positive predictive value of 80%. 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.
Revvity Omics, Revvity RCV000808945 SCV003832138 uncertain significance Combined immunodeficiency due to DOCK8 deficiency 2019-07-31 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000766471 SCV004161707 likely benign not provided 2023-09-01 criteria provided, single submitter clinical testing DOCK8: BP4
PreventionGenetics, part of Exact Sciences RCV003947716 SCV004760711 uncertain significance DOCK8-related disorder 2024-01-28 criteria provided, single submitter clinical testing The DOCK8 c.2017A>T variant is predicted to result in the amino acid substitution p.Ile673Phe. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.026% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.