chr19-11202580-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020812.4(DOCK6):c.5361+4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 1,613,742 control chromosomes in the GnomAD database, including 132,124 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10249 hom., cov: 32)

Exomes 𝑓: 0.41 ( 121875 hom. )

Consequence

DOCK6
NM_020812.4 splice_region, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.20

Publications

22 publications found

Variant links:

Genes affected

DOCK6 (HGNC:19189): (dedicator of cytokinesis 6) This gene encodes a member of the dedicator of cytokinesis (DOCK) family of atypical guanine nucleotide exchange factors. Guanine nucleotide exchange factors interact with small GTPases and are components of intracellular signaling networks. The encoded protein is a group C DOCK protein and plays a role in actin cytoskeletal reorganization by activating the Rho GTPases Cdc42 and Rac1. Mutations in this gene are associated with Adams-Oliver syndrome 2. [provided by RefSeq, Dec 2011]

DOCK6 links:

DOCK6-AS1 (HGNC:56684): (DOCK6 antisense RNA 1)

DOCK6-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 19-11202580-G-A is Benign according to our data. Variant chr19-11202580-G-A is described in ClinVar as Benign. ClinVar VariationId is 261358.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK6	NM_020812.4 link	c.5361+4C>T		splice_region_variant, intron_variant	Intron 42 of 47	ENST00000294618.12	NP_065863.2	Q96HP0B7Z9U8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK6	ENST00000294618.12 link	c.5361+4C>T		splice_region_variant, intron_variant	Intron 42 of 47	1	NM_020812.4	ENSP00000294618.6		Q96HP0

Frequencies

GnomAD3 genomes

AF:

0.359

AC:

54543

AN:

151988

Hom.:

10249

Cov.:

show subpopulations

Gnomad AFR

AF:

0.243

Gnomad AMI

AF:

0.565

Gnomad AMR

AF:

0.371

Gnomad ASJ

AF:

0.338

Gnomad EAS

AF:

0.373

Gnomad SAS

AF:

0.470

Gnomad FIN

AF:

0.465

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.399

Gnomad OTH

AF:

0.359

GnomAD2 exomes

AF:

0.394

AC:

98152

AN:

248936

AF XY:

0.401

show subpopulations

Gnomad AFR exome

AF:

0.234

Gnomad AMR exome

AF:

0.372

Gnomad ASJ exome

AF:

0.348

Gnomad EAS exome

AF:

0.367

Gnomad FIN exome

AF:

0.461

Gnomad NFE exome

AF:

0.399

Gnomad OTH exome

AF:

0.399

GnomAD4 exome

AF:

0.406

AC:

594037

AN:

1461636

Hom.:

121875

Cov.:

AF XY:

0.409

AC XY:

297103

AN XY:

727102

show subpopulations

African (AFR)

AF:

0.227

AC:

7611

AN:

33480

American (AMR)

AF:

0.373

AC:

16695

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.345

AC:

9009

AN:

26136

East Asian (EAS)

AF:

0.379

AC:

15036

AN:

39700

South Asian (SAS)

AF:

0.468

AC:

40344

AN:

86258

European-Finnish (FIN)

AF:

0.460

AC:

24539

AN:

53336

Middle Eastern (MID)

AF:

0.357

AC:

2059

AN:

5768

European-Non Finnish (NFE)

AF:

0.409

AC:

454438

AN:

1111862

Other (OTH)

AF:

0.403

AC:

24306

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

24499

48999

73498

97998

122497

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14114

28228

42342

56456

70570

<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:

0.359

AC:

54563

AN:

152106

Hom.:

10249

Cov.:

AF XY:

0.363

AC XY:

26937

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.243

AC:

10106

AN:

41518

American (AMR)

AF:

0.371

AC:

5673

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.338

AC:

1175

AN:

3472

East Asian (EAS)

AF:

0.374

AC:

1927

AN:

5150

South Asian (SAS)

AF:

0.469

AC:

2266

AN:

4828

European-Finnish (FIN)

AF:

0.465

AC:

4902

AN:

10546

Middle Eastern (MID)

AF:

0.432

AC:

127

AN:

294

European-Non Finnish (NFE)

AF:

0.399

AC:

27120

AN:

67986

Other (OTH)

AF:

0.357

AC:

752

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1780

3561

5341

7122

8902

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

548

1096

1644

2192

2740

<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:

0.380

Hom.:

23076

Bravo

AF:

0.346

Asia WGS

AF:

0.421

AC:

1458

AN:

3478

EpiCase

AF:

0.394

EpiControl

AF:

0.393

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Nov 08, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:2

Apr 19, 2016

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Adams-Oliver syndrome 2

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.17

(source)

DANN

Benign

0.74

PhyloP100

-1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over