Variant 9-289590-CTTT-CTT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_203447.4(DOCK8):c.404+16delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0322 in 1,607,164 control chromosomes in the GnomAD database, including 1,012 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 96 hom., cov: 32)

Exomes 𝑓: 0.032 ( 916 hom. )

Consequence

DOCK8
NM_203447.4 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.667

Variant links:

Genes affected

DOCK8 (HGNC:19191): (dedicator of cytokinesis 8) This gene encodes a member of the DOCK180 family of guanine nucleotide exchange factors. Guanine nucleotide exchange factors interact with Rho GTPases and are components of intracellular signaling networks. Mutations in this gene result in the autosomal recessive form of the hyper-IgE syndrome. Alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Jun 2010]

DOCK8 links:

DOCK8 (HGNC:):

DOCK8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 9-289590-CT-C is Benign according to our data. Variant chr9-289590-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 180037.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-289590-CT-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK8	NM_203447.4 linkuse as main transcript	c.404+16delT		intron_variant		ENST00000432829.7	NP_982272.2	Q8NF50-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK8	ENST00000432829.7 linkuse as main transcript	c.404+16delT		intron_variant		1	NM_203447.4	ENSP00000394888.3		Q8NF50-1

Frequencies

GnomAD3 genomes

AF:

0.0306

AC:

4647

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0280

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.0251

Gnomad ASJ

AF:

0.0660

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0588

Gnomad FIN

AF:

0.0154

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0328

Gnomad OTH

AF:

0.0273

GnomAD3 exomes

AF:

0.0320

AC:

7986

AN:

249946

Hom.:

192

AF XY:

0.0345

AC XY:

4667

AN XY:

135088

show subpopulations

Gnomad AFR exome

AF:

0.0301

Gnomad AMR exome

AF:

0.0159

Gnomad ASJ exome

AF:

0.0652

Gnomad EAS exome

AF:

0.000549

Gnomad SAS exome

AF:

0.0642

Gnomad FIN exome

AF:

0.0159

Gnomad NFE exome

AF:

0.0337

Gnomad OTH exome

AF:

0.0303

GnomAD4 exome

AF:

0.0324

AC:

47176

AN:

1454954

Hom.:

916

Cov.:

AF XY:

0.0338

AC XY:

24453

AN XY:

723590

show subpopulations

Gnomad4 AFR exome

AF:

0.0286

Gnomad4 AMR exome

AF:

0.0157

Gnomad4 ASJ exome

AF:

0.0623

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0626

Gnomad4 FIN exome

AF:

0.0165

Gnomad4 NFE exome

AF:

0.0322

Gnomad4 OTH exome

AF:

0.0303

GnomAD4 genome

AF:

0.0306

AC:

4655

AN:

152210

Hom.:

Cov.:

AF XY:

0.0304

AC XY:

2262

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0282

Gnomad4 AMR

AF:

0.0250

Gnomad4 ASJ

AF:

0.0660

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.0585

Gnomad4 FIN

AF:

0.0154

Gnomad4 NFE

AF:

0.0328

Gnomad4 OTH

AF:

0.0270

Bravo

AF:

0.0298

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Sep 02, 2015	c.404+16delT in intron 4 of DOCK8: This variant is not expected to have clinical significance because it has been identified in 3.64% (2389/65588) of European c hromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute .org; dbSNP rs202087573). -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Hyper-IgE syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Autosomal recessive hyper-IgE syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over