9-463276-TAA-T

Position:

• chr9-463276-TAA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_203447.4(DOCK8):​c.6069-230_6069-229delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.24 (4534 hom., cov: 0)
• Consequence: DOCK8 NM_203447.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.332

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 -10 ACMG points.

• BP6: Variant 9-463276-TAA-T is Benign according to our data. Variant chr9-463276-TAA-T is described in ClinVar as [Benign]. Clinvar id is 1180172.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK8	NM_203447.4	c.6069-230_6069-229delAA		intron_variant		ENST00000432829.7	NP_982272.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK8	ENST00000432829.7	c.6069-230_6069-229delAA		intron_variant		1	NM_203447.4	ENSP00000394888.3

Frequencies

GnomAD3 genomes AF: 0.240 AC: 35604 AN: 148478 Hom.: 4516 Cov.: 0

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.240 AC: 35660 AN: 148576 Hom.: 4534 Cov.: 0 AF XY: 0.246 AC XY: 17814 AN XY: 72386

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.255

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 29, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs5895846; hg19: chr9-463276;