Submissions for variant NM_203447.4(DOCK8):c.3058A>G (p.Ile1020Val)

gnomAD frequency: 0.00046  dbSNP: rs151094543

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000202995	SCV000258288	benign	not specified	2015-07-24	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000645157	SCV000480258	uncertain significance	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV001697210	SCV000532250	likely benign	not provided	2018-07-20	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 32108967)
Invitae	RCV003761826	SCV000766899	benign	Autosomal recessive hyper-IgE syndrome	2024-01-25	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003401098	SCV004103340	uncertain significance	DOCK8-related disorder	2022-11-21	criteria provided, single submitter	clinical testing	The DOCK8 c.3058A>G variant is predicted to result in the amino acid substitution p.Ile1020Val. This variant was reported in the homozygous state in two individuals with DOCK8 deficiency (reported as rs151094543 in Table 1, Haskologlu et al 2020. PubMed ID: 32108967). This variant in interpreted as benign/likely benign/uncertain in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/218873/). This variant is reported in 0.091% of alleles in individuals of South Asian descent, including two homozygotes, in gnomAD (http://gnomad.broadinstitute.org/variant/9-396872-A-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
CeGaT Center for Human Genetics Tuebingen	RCV001697210	SCV004161713	likely benign	not provided	2023-07-01	criteria provided, single submitter	clinical testing	DOCK8: BP4