rs12978266

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.749C>T(p.Pro250Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.671 in 1,610,060 control chromosomes in the GnomAD database, including 373,583 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 26704 hom., cov: 31)

Exomes 𝑓: 0.68 ( 346879 hom. )

Consequence

DOCK6
NM_020812.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 7.73

Publications

39 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 Gene-Disease associations (from GenCC):

Adams-Oliver syndrome
Inheritance: AD, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
Adams-Oliver syndrome 2
Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

DOCK6 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 (MetaRNN=2.1588268E-5).

BP6

Variant 19-11248123-G-A is Benign according to our data. Variant chr19-11248123-G-A is described in ClinVar as [Benign]. Clinvar id is 261359.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK6	NM_020812.4 link	c.749C>T	p.Pro250Leu	missense_variant	Exon 7 of 48	ENST00000294618.12	NP_065863.2	Q96HP0B7Z9U8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DOCK6	ENST00000294618.12 link	c.749C>T	p.Pro250Leu	missense_variant	Exon 7 of 48	1	NM_020812.4	ENSP00000294618.6	Q96HP0
DOCK6	ENST00000587656.6 link	c.749C>T	p.Pro250Leu	missense_variant	Exon 7 of 49	5		ENSP00000468638.2	K7ESB7
DOCK6	ENST00000585609.1 link	n.2287C>T		non_coding_transcript_exon_variant	Exon 4 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.551

AC:

83599

AN:

151848

Hom.:

26704

Cov.:

show subpopulations

Gnomad AFR

AF:

0.205

Gnomad AMI

AF:

0.752

Gnomad AMR

AF:

0.610

Gnomad ASJ

AF:

0.782

Gnomad EAS

AF:

0.529

Gnomad SAS

AF:

0.708

Gnomad FIN

AF:

0.665

Gnomad MID

AF:

0.763

Gnomad NFE

AF:

0.703

Gnomad OTH

AF:

0.613

GnomAD2 exomes

AF:

0.640

AC:

156330

AN:

244156

AF XY:

0.658

show subpopulations

Gnomad AFR exome

AF:

0.187

Gnomad AMR exome

AF:

0.567

Gnomad ASJ exome

AF:

0.762

Gnomad EAS exome

AF:

0.508

Gnomad FIN exome

AF:

0.667

Gnomad NFE exome

AF:

0.705

Gnomad OTH exome

AF:

0.696

GnomAD4 exome

AF:

0.684

AC:

997033

AN:

1458094

Hom.:

346879

Cov.:

AF XY:

0.687

AC XY:

498272

AN XY:

725066

show subpopulations

African (AFR)

AF:

0.182

AC:

6098

AN:

33446

American (AMR)

AF:

0.576

AC:

25494

AN:

44270

Ashkenazi Jewish (ASJ)

AF:

0.760

AC:

19782

AN:

26034

East Asian (EAS)

AF:

0.526

AC:

20845

AN:

39616

South Asian (SAS)

AF:

0.719

AC:

61570

AN:

85668

European-Finnish (FIN)

AF:

0.665

AC:

35196

AN:

52904

Middle Eastern (MID)

AF:

0.762

AC:

4385

AN:

5756

European-Non Finnish (NFE)

AF:

0.706

AC:

783327

AN:

1110136

Other (OTH)

AF:

0.669

AC:

40336

AN:

60264

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

13884

27768

41652

55536

69420

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.550

AC:

83620

AN:

151966

Hom.:

26704

Cov.:

AF XY:

0.551

AC XY:

40919

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.205

AC:

8495

AN:

41472

American (AMR)

AF:

0.610

AC:

9311

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.782

AC:

2713

AN:

3470

East Asian (EAS)

AF:

0.530

AC:

2726

AN:

5144

South Asian (SAS)

AF:

0.709

AC:

3417

AN:

4818

European-Finnish (FIN)

AF:

0.665

AC:

7012

AN:

10550

Middle Eastern (MID)

AF:

0.759

AC:

223

AN:

294

European-Non Finnish (NFE)

AF:

0.703

AC:

47754

AN:

67940

Other (OTH)

AF:

0.611

AC:

1285

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1557

3115

4672

6230

7787

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.657

Hom.:

108367

Bravo

AF:

0.527

TwinsUK

AF:

0.703

AC:

2608

ALSPAC

AF:

0.694

AC:

2675

ESP6500AA

AF:

0.236

AC:

916

ESP6500EA

AF:

0.701

AC:

5789

ExAC

AF:

0.632

AC:

76379

Asia WGS

AF:

0.603

AC:

2097

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Adams-Oliver syndrome 2

Benign:3

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Oct 16, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 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

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.99

MetaRNN

Benign

0.000022

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

PhyloP100

7.7

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-7.9

REVEL

Benign

0.20

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0050

Polyphen

0.98

Vest4

0.21

MPC

0.24

ClinPred

0.082

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.59

gMVP

0.62

Mutation Taster

=90/10

polymorphism (auto)

(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.

rs12978266

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