rs10813766

Positions:

• chr9-331490-T-G

Variant summary

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

The NM_203447.4(DOCK8):​c.1045-908T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 152,120 control chromosomes in the GnomAD database, including 31,363 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 0.64 (31363 hom., cov: 33)
• Consequence: DOCK8 NM_203447.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.987

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK8	NM_203447.4	c.1045-908T>G		intron_variant		ENST00000432829.7	NP_982272.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK8	ENST00000432829.7	c.1045-908T>G		intron_variant		1	NM_203447.4	ENSP00000394888.3

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97375 AN: 152002 Hom.: 31355 Cov.: 33

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.613

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

GnomAD4 genome AF: 0.640 AC: 97411 AN: 152120 Hom.: 31363 Cov.: 33 AF XY: 0.643 AC XY: 47778 AN XY: 74352

Gnomad4 AFR AF: 0.605

Gnomad4 AMR AF: 0.631

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.711

Gnomad4 SAS AF: 0.757

Gnomad4 FIN AF: 0.652

Gnomad4 NFE AF: 0.653

Gnomad4 OTH AF: 0.618

Alfa AF: 0.645 Hom.: 62545

Bravo AF: 0.634

Asia WGS AF: 0.732 AC: 2544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.2
DANN	Benign	0.82

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: rs10813766; hg19: chr9-331490;