Genetic Variant DOCK8:c.-152+3531A>C (chr9-214847-A-C) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NR_160804.1(DOCK8-AS1):n.904T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000817 in 1,601,674 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 4 hom., cov: 34)

Exomes 𝑓: 0.00049 ( 3 hom. )

Consequence

DOCK8-AS1
NR_160804.1 non_coding_transcript_exon

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.78

Publications

1 publications found

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:26436): (DOCK8 antisense RNA 1)

DOCK8-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0052739084).

BP6

Variant 9-214847-A-C is Benign according to our data. Variant chr9-214847-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1321799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_160804.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK8-AS1	NR_160804.1		n.904T>G		non_coding_transcript_exon	Exon 1 of 1
	DOCK8	NM_203447.4	MANE Select	c.-130A>C		upstream_gene	N/A	NP_982272.2	Q8NF50-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DOCK8-AS1	ENST00000382387.4	TSL:6	n.1047T>G	non_coding_transcript_exon	Exon 1 of 1
DOCK8-AS1	ENST00000648587.1		n.895T>G	non_coding_transcript_exon	Exon 1 of 1
DOCK8	ENST00000432829.7	TSL:1 MANE Select	c.-130A>C	upstream_gene	N/A	ENSP00000394888.3	Q8NF50-1

Frequencies

GnomAD3 genomes

AF:

0.00393

AC:

598

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0136

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000883

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000993

AC:

231

AN:

232618

AF XY:

0.000733

show subpopulations

Gnomad AFR exome

AF:

0.0135

Gnomad AMR exome

AF:

0.00115

Gnomad ASJ exome

AF:

0.000314

Gnomad EAS exome

AF:

0.000291

Gnomad FIN exome

AF:

0.0000471

Gnomad NFE exome

AF:

0.0000863

Gnomad OTH exome

AF:

0.000701

GnomAD4 exome

AF:

0.000488

AC:

708

AN:

1449512

Hom.:

Cov.:

AF XY:

0.000402

AC XY:

290

AN XY:

721102

show subpopulations

African (AFR)

AF:

0.0153

AC:

490

AN:

32120

American (AMR)

AF:

0.00120

AC:

AN:

44010

Ashkenazi Jewish (ASJ)

AF:

0.000233

AC:

AN:

25800

East Asian (EAS)

AF:

0.00129

AC:

AN:

38786

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84822

European-Finnish (FIN)

AF:

0.0000193

AC:

AN:

51858

Middle Eastern (MID)

AF:

0.000349

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.0000470

AC:

AN:

1106396

Other (OTH)

AF:

0.000884

AC:

AN:

59982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

139

186

232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00395

AC:

601

AN:

152162

Hom.:

Cov.:

AF XY:

0.00348

AC XY:

259

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.0136

AC:

566

AN:

41524

American (AMR)

AF:

0.00137

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3470

East Asian (EAS)

AF:

0.000387

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000883

AC:

AN:

67974

Other (OTH)

AF:

0.00142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

119

149

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000672

Hom.:

Bravo

AF:

0.00529

ESP6500AA

AF:

0.0102

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00115

AC:

135

Asia WGS

AF:

0.00116

AC:

AN:

3474

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.0095

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.23

MetaRNN

Benign

0.0053

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

2.8

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.18

Sift4G

Benign

0.99

Polyphen

0.99

Vest4

0.43

MVP

0.24

MPC

0.17

ClinPred

0.040

GERP RS

4.9

PromoterAI

-0.80

Under-expression

(source)

Varity_R

0.64

gMVP

0.010

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over