rs6476030

Positions:

• chr9-289061-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_203447.4(DOCK8):​c.333-449A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0687 in 152,278 control chromosomes in the GnomAD database, including 618 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.069 (618 hom., cov: 33)
• Consequence: DOCK8 NM_203447.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK8	NM_203447.4	c.333-449A>G		intron_variant		ENST00000432829.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK8	ENST00000432829.7	c.333-449A>G		intron_variant		1	NM_203447.4

Frequencies

GnomAD3 genomes AF: 0.0686 AC: 10431 AN: 152160 Hom.: 614 Cov.: 33

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0693

Gnomad ASJ AF: 0.0374

Gnomad EAS AF: 0.0164

Gnomad SAS AF: 0.0333

Gnomad FIN AF: 0.0143

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0279

Gnomad OTH AF: 0.0588

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0687 AC: 10459 AN: 152278 Hom.: 618 Cov.: 33 AF XY: 0.0663 AC XY: 4934 AN XY: 74472

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.0692

Gnomad4 ASJ AF: 0.0374

Gnomad4 EAS AF: 0.0164

Gnomad4 SAS AF: 0.0334

Gnomad4 FIN AF: 0.0143

Gnomad4 NFE AF: 0.0279

Gnomad4 OTH AF: 0.0591

Alfa AF: 0.0382 Hom.: 285

Bravo AF: 0.0776

Asia WGS AF: 0.0440 AC: 156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.81
DANN	Benign	0.68

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

Other links and lift over

dbSNP: rs6476030; hg19: chr9-289061;