Variant chr19-11252470-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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:6

Conservation

PhyloP100: -0.595

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 261356.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11252470-A-T is described in Lovd as [Benign].

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/exons	MANE	UniProt
DOCK6	NM_020812.4 linkuse as main transcript	c.377+12T>A		intron_variant		ENST00000294618.12

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
DOCK6	ENST00000294618.12 linkuse as main transcript	c.377+12T>A	intron_variant		1	NM_020812.4	A2
DOCK6	ENST00000587656.6 linkuse as main transcript	c.377+12T>A	intron_variant		5		P3
DOCK6	ENST00000585609.1 linkuse as main transcript	n.662T>A	non_coding_transcript_exon_variant	3/4	2
DOCK6	ENST00000586482.1 linkuse as main transcript	n.286T>A	non_coding_transcript_exon_variant	3/3	3

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

GnomAD3 exomes

AF:

0.699

AC:

173969

AN:

248786

Hom.:

62796

AF XY:

0.714

AC XY:

96373

AN XY:

135060

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 SAS exome

AF:

0.744

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

Gnomad4 AFR exome

AF:

0.253

Gnomad4 AMR exome

AF:

0.636

Gnomad4 ASJ exome

AF:

0.769

Gnomad4 EAS exome

AF:

0.675

Gnomad4 SAS exome

AF:

0.743

Gnomad4 FIN exome

AF:

0.728

Gnomad4 NFE exome

AF:

0.759

Gnomad4 OTH exome

AF:

0.721

GnomAD4 genome

AF:

0.609

AC:

92632

AN:

152068

Hom.:

31568

Cov.:

AF XY:

0.610

AC XY:

45323

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.275

Gnomad4 AMR

AF:

0.659

Gnomad4 ASJ

AF:

0.790

Gnomad4 EAS

AF:

0.662

Gnomad4 SAS

AF:

0.740

Gnomad4 FIN

AF:

0.730

Gnomad4 NFE

AF:

0.755

Gnomad4 OTH

AF:

0.663

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:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Adams-Oliver syndrome 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.71

DANN

Benign

0.48

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.0

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