Variant 19-11199430-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020812.4(DOCK6):c.*67G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00629 in 1,543,122 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0065 ( 45 hom. )

Consequence

DOCK6
NM_020812.4 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.171

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004704863).

BP6

Variant 19-11199430-C-T is Benign according to our data. Variant chr19-11199430-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1707391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00406 (619/152388) while in subpopulation SAS AF= 0.0124 (60/4832). AF 95% confidence interval is 0.0099. There are 4 homozygotes in gnomad4. There are 278 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK6	NM_020812.4 linkuse as main transcript	c.*67G>A		3_prime_UTR_variant	48/48	ENST00000294618.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
DOCK6	ENST00000294618.12 linkuse as main transcript	c.*67G>A		3_prime_UTR_variant	48/48	1	NM_020812.4	A2
DOCK6	ENST00000587734.1 linkuse as main transcript	c.185G>A	p.Gly62Glu	missense_variant	2/2	5
DOCK6	ENST00000586702.1 linkuse as main transcript	n.1114G>A		non_coding_transcript_exon_variant	7/7	2

Frequencies

GnomAD3 genomes

AF:

0.00407

AC:

619

AN:

152270

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00137

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0124

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00644

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00471

AC:

742

AN:

157612

Hom.:

AF XY:

0.00553

AC XY:

461

AN XY:

83344

show subpopulations

Gnomad AFR exome

AF:

0.000989

Gnomad AMR exome

AF:

0.00198

Gnomad ASJ exome

AF:

0.000117

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0126

Gnomad FIN exome

AF:

0.000664

Gnomad NFE exome

AF:

0.00609

Gnomad OTH exome

AF:

0.00249

GnomAD4 exome

AF:

0.00654

AC:

9089

AN:

1390734

Hom.:

Cov.:

AF XY:

0.00663

AC XY:

4554

AN XY:

686578

show subpopulations

Gnomad4 AFR exome

AF:

0.000795

Gnomad4 AMR exome

AF:

0.00221

Gnomad4 ASJ exome

AF:

0.0000397

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0122

Gnomad4 FIN exome

AF:

0.000547

Gnomad4 NFE exome

AF:

0.00713

Gnomad4 OTH exome

AF:

0.00588

GnomAD4 genome

AF:

0.00406

AC:

619

AN:

152388

Hom.:

Cov.:

AF XY:

0.00373

AC XY:

278

AN XY:

74526

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0124

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.00644

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00423

Hom.:

Bravo

AF:

0.00363

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00934

AC:

ESP6500AA

AF:

0.00289

AC:

ESP6500EA

AF:

0.00817

AC:

ExAC

AF:

0.00251

AC:

258

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	DOCK6: BS1, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 18, 2020	See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.89

Cadd

Benign

4.0

Dann

Benign

0.46

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.29

MetaRNN

Benign

0.0047

MutationTaster

Benign

1.0

N;N

MVP

0.63

GERP RS

-0.26

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