Variant chr19-11236817-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020812.4(DOCK6):c.2136A>G(p.Thr712=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,553,570 control chromosomes in the GnomAD database, including 15,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 4814 hom., cov: 32)

Exomes 𝑓: 0.10 ( 10987 hom. )

Consequence

DOCK6
NM_020812.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.24

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 19-11236817-T-C is Benign according to our data. Variant chr19-11236817-T-C is described in ClinVar as [Benign]. Clinvar id is 1170730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11236817-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.24 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.424 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.2136A>G	p.Thr712=	synonymous_variant	19/48	ENST00000294618.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
DOCK6	ENST00000294618.12 linkuse as main transcript	c.2136A>G	p.Thr712=	synonymous_variant	19/48	1	NM_020812.4	A2
DOCK6	ENST00000587656.6 linkuse as main transcript	c.2136A>G	p.Thr712=	synonymous_variant	19/49	5		P3
DOCK6	ENST00000590680.5 linkuse as main transcript	c.480A>G	p.Thr160=	synonymous_variant	5/11	5
DOCK6	ENST00000591750.1 linkuse as main transcript	n.2105A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30275

AN:

151990

Hom.:

4799

Cov.:

show subpopulations

Gnomad AFR

AF:

0.429

Gnomad AMI

AF:

0.121

Gnomad AMR

AF:

0.221

Gnomad ASJ

AF:

0.0233

Gnomad EAS

AF:

0.255

Gnomad SAS

AF:

0.158

Gnomad FIN

AF:

0.0847

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0830

Gnomad OTH

AF:

0.167

GnomAD3 exomes

AF:

0.151

AC:

23987

AN:

158802

Hom.:

2824

AF XY:

0.141

AC XY:

11908

AN XY:

84448

show subpopulations

Gnomad AFR exome

AF:

0.437

Gnomad AMR exome

AF:

0.283

Gnomad ASJ exome

AF:

0.0285

Gnomad EAS exome

AF:

0.262

Gnomad SAS exome

AF:

0.146

Gnomad FIN exome

AF:

0.0894

Gnomad NFE exome

AF:

0.0779

Gnomad OTH exome

AF:

0.118

GnomAD4 exome

AF:

0.101

AC:

142035

AN:

1401462

Hom.:

10987

Cov.:

AF XY:

0.102

AC XY:

70294

AN XY:

691542

show subpopulations

Gnomad4 AFR exome

AF:

0.447

Gnomad4 AMR exome

AF:

0.272

Gnomad4 ASJ exome

AF:

0.0278

Gnomad4 EAS exome

AF:

0.264

Gnomad4 SAS exome

AF:

0.150

Gnomad4 FIN exome

AF:

0.0900

Gnomad4 NFE exome

AF:

0.0782

Gnomad4 OTH exome

AF:

0.114

GnomAD4 genome

AF:

0.199

AC:

30342

AN:

152108

Hom.:

4814

Cov.:

AF XY:

0.201

AC XY:

14942

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.429

Gnomad4 AMR

AF:

0.221

Gnomad4 ASJ

AF:

0.0233

Gnomad4 EAS

AF:

0.254

Gnomad4 SAS

AF:

0.157

Gnomad4 FIN

AF:

0.0847

Gnomad4 NFE

AF:

0.0830

Gnomad4 OTH

AF:

0.170

Alfa

AF:

0.104

Hom.:

3370

Bravo

AF:

0.223

Asia WGS

AF:

0.199

AC:

694

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.21

DANN

Benign

0.42

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