Submissions for variant NM_203447.4(DOCK8):c.4024-4C>T

gnomAD frequency: 0.00196  dbSNP: rs111306749

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000905669	SCV000480298	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000601801	SCV000711312	benign	not specified	2017-03-06	criteria provided, single submitter	clinical testing	c.4024-4C>T in intron 31 of DOCK8: This variant is not expected to have clinical significance because it is not located within the splice consensus sequence. It has been identified in 1.3% (88/6614) of European (Finnish) chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs1113 06749).
GeneDx	RCV000601801	SCV000731055	likely benign	not specified	2017-05-19	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV003595949	SCV001050261	benign	Autosomal recessive hyper-IgE syndrome	2024-01-25	criteria provided, single submitter	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001573987	SCV001800645	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001573987	SCV001927223	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001573987	SCV001975795	likely benign	not provided		no assertion criteria provided	clinical testing