19-11252470-A-T

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.377+12T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 1,613,360 control chromosomes in the GnomAD database, including 434,794 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.61 ( 31568 hom., cov: 32)

Exomes 𝑓: 0.74 ( 403226 hom. )

Consequence

DOCK6
NM_020812.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.595

Publications

13 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 (BayesDel_noAF=-0.87).

BP6

Variant 19-11252470-A-T is Benign according to our data. Variant chr19-11252470-A-T is described in ClinVar as Benign. ClinVar VariationId is 261356.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK6	NM_020812.4 link	c.377+12T>A		intron_variant	Intron 4 of 47	ENST00000294618.12	NP_065863.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
DOCK6	ENST00000294618.12 link	c.377+12T>A	intron_variant	Intron 4 of 47	1	NM_020812.4	ENSP00000294618.6
DOCK6	ENST00000585609.1 link	n.662T>A	non_coding_transcript_exon_variant	Exon 3 of 4	2
DOCK6	ENST00000586482.1 link	n.286T>A	non_coding_transcript_exon_variant	Exon 3 of 3	3
DOCK6	ENST00000587656.6 link	c.377+12T>A	intron_variant	Intron 4 of 48	5		ENSP00000468638.2

Frequencies

GnomAD3 genomes

AF:

0.609

AC:

92586

AN:

151950

Hom.:

31559

Cov.:

show subpopulations

Gnomad AFR

AF:

0.275

Gnomad AMI

AF:

0.810

Gnomad AMR

AF:

0.658

Gnomad ASJ

AF:

0.790

Gnomad EAS

AF:

0.662

Gnomad SAS

AF:

0.739

Gnomad FIN

AF:

0.730

Gnomad MID

AF:

0.791

Gnomad NFE

AF:

0.755

Gnomad OTH

AF:

0.660

GnomAD2 exomes

AF:

0.699

AC:

173969

AN:

248786

AF XY:

0.714

show subpopulations

Gnomad AFR exome

AF:

0.258

Gnomad AMR exome

AF:

0.629

Gnomad ASJ exome

AF:

0.773

Gnomad EAS exome

AF:

0.649

Gnomad FIN exome

AF:

0.730

Gnomad NFE exome

AF:

0.762

Gnomad OTH exome

AF:

0.751

GnomAD4 exome

AF:

0.738

AC:

1078642

AN:

1461292

Hom.:

403226

Cov.:

AF XY:

0.741

AC XY:

538319

AN XY:

726932

show subpopulations

African (AFR)

AF:

0.253

AC:

8457

AN:

33476

American (AMR)

AF:

0.636

AC:

28457

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.769

AC:

20111

AN:

26136

East Asian (EAS)

AF:

0.675

AC:

26800

AN:

39700

South Asian (SAS)

AF:

0.743

AC:

64084

AN:

86248

European-Finnish (FIN)

AF:

0.728

AC:

38778

AN:

53230

Middle Eastern (MID)

AF:

0.775

AC:

4467

AN:

5766

European-Non Finnish (NFE)

AF:

0.759

AC:

843955

AN:

1111652

Other (OTH)

AF:

0.721

AC:

43533

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

15436

30872

46307

61743

77179

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20232

40464

60696

80928

101160

<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:

0.609

AC:

92632

AN:

152068

Hom.:

31568

Cov.:

AF XY:

0.610

AC XY:

45323

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.275

AC:

11399

AN:

41466

American (AMR)

AF:

0.659

AC:

10062

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.790

AC:

2740

AN:

3470

East Asian (EAS)

AF:

0.662

AC:

3418

AN:

5160

South Asian (SAS)

AF:

0.740

AC:

3559

AN:

4810

European-Finnish (FIN)

AF:

0.730

AC:

7722

AN:

10574

Middle Eastern (MID)

AF:

0.789

AC:

232

AN:

294

European-Non Finnish (NFE)

AF:

0.755

AC:

51365

AN:

67994

Other (OTH)

AF:

0.663

AC:

1398

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1532

3064

4596

6128

7660

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

754

1508

2262

3016

3770

<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:

0.694

Hom.:

7125

Bravo

AF:

0.586

Asia WGS

AF:

0.709

AC:

2464

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

- -

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

- -

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

-0.87

CADD

Benign

0.71

(source)

DANN

Benign

0.48

PhyloP100

-0.59

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.0

Mutation Taster

=100/0

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

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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