Submissions for variant NM_203447.4(DOCK8):c.494C>T (p.Ser165Leu)

gnomAD frequency: 0.00061  dbSNP: rs146490788

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000768199	SCV000479547	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	RCV000762542	SCV000576542	uncertain significance	not provided	2021-03-19	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32084423)
CeGaT Center for Human Genetics Tuebingen	RCV000762542	SCV000892872	likely benign	not provided	2025-01-01	criteria provided, single submitter	clinical testing	DOCK8: BS2
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000768199	SCV000898650	uncertain significance	Combined immunodeficiency due to DOCK8 deficiency	2021-03-30	criteria provided, single submitter	clinical testing	DOCK8 NM_203447 exon 5 p.Ser165Leu (c.494C>T): This variant has not been reported in the literature but is present in 0.2% (28/10150) of Ashkenazi Jewish alleles, including 1 homozygote in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs146490788). This variant is present in ClinVar (Variation ID:366541). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp	RCV005090614	SCV000932479	likely benign	not provided	2024-12-31	criteria provided, single submitter	clinical testing
New York Genome Center	RCV000768199	SCV001622930	uncertain significance	Combined immunodeficiency due to DOCK8 deficiency	2020-07-09	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000762542	SCV001927889	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000762542	SCV001967714	likely benign	not provided		no assertion criteria provided	clinical testing