Variant 9-214679-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The XM_047423927.1(DOCK8):c.-152+3363G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,585,830 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 32 hom. )

Consequence

DOCK8
XM_047423927.1 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.461

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-AS1 (HGNC:):

DOCK8-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003052324).

BP6

Variant 9-214679-G-A is Benign according to our data. Variant chr9-214679-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1187835.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00143 (217/152262) while in subpopulation EAS AF= 0.0364 (188/5158). AF 95% confidence interval is 0.0322. There are 3 homozygotes in gnomad4. There are 131 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein	UniProt
DOCK8	XM_047423927.1 linkuse as main transcript	c.-152+3363G>A	intron_variant	XP_047279883.1
DOCK8	XM_017015173.2 linkuse as main transcript	c.-152+3363G>A	intron_variant	XP_016870662.1	Q8NF50-3
DOCK8	XM_047423930.1 linkuse as main transcript	c.-152+3363G>A	intron_variant	XP_047279886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK8-AS1	ENST00000382387.4 linkuse as main transcript	n.1215C>T		non_coding_transcript_exon_variant	1/1	6
DOCK8-AS1	ENST00000648587.1 linkuse as main transcript	n.1063C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.00144

AC:

219

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0367

Gnomad SAS

AF:

0.00434

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00294

AC:

559

AN:

190002

Hom.:

AF XY:

0.00284

AC XY:

298

AN XY:

104830

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000209

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0380

Gnomad SAS exome

AF:

0.000731

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000127

Gnomad OTH exome

AF:

0.00260

GnomAD4 exome

AF:

0.00114

AC:

1639

AN:

1433568

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

781

AN XY:

711128

show subpopulations

Gnomad4 AFR exome

AF:

0.0000307

Gnomad4 AMR exome

AF:

0.000124

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0338

Gnomad4 SAS exome

AF:

0.00112

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000173

Gnomad4 OTH exome

AF:

0.00402

GnomAD4 genome

AF:

0.00143

AC:

217

AN:

152262

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

131

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0364

Gnomad4 SAS

AF:

0.00435

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000370

Hom.:

Bravo

AF:

0.00172

ExAC

AF:

0.00232

AC:

262

Asia WGS

AF:

0.0210

AC:

AN:

3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.058

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.35

MetaRNN

Benign

0.0031

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PROVEAN

Pathogenic

-7.0

REVEL

Benign

0.10

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.037

MVP

0.067

MPC

0.48

ClinPred

0.18

GERP RS

0.38

Varity_R

0.73

gMVP

0.018

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