rs112911897

Positions:

chr19-11215909-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_020812.4(DOCK6):c.3913C>T(p.Arg1305Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00972 in 1,613,744 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0078 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0099 ( 94 hom. )

Consequence

DOCK6
NM_020812.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.640

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:

DOCK6 (HGNC:):

DOCK6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 19-11215909-G-A is Benign according to our data. Variant chr19-11215909-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 445548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11215909-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00782 (1190/152134) while in subpopulation NFE AF= 0.0109 (740/68014). AF 95% confidence interval is 0.0102. There are 7 homozygotes in gnomad4. There are 614 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK6	NM_020812.4 linkuse as main transcript	c.3913C>T	p.Arg1305Cys	missense_variant	31/48	ENST00000294618.12	NP_065863.2	Q96HP0B7Z9U8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DOCK6	ENST00000294618.12 linkuse as main transcript	c.3913C>T	p.Arg1305Cys	missense_variant	31/48	1	NM_020812.4	ENSP00000294618.6	Q96HP0
DOCK6	ENST00000587656.6 linkuse as main transcript	c.4018C>T	p.Arg1340Cys	missense_variant	32/49	5		ENSP00000468638.2	K7ESB7
DOCK6	ENST00000588429.1 linkuse as main transcript	n.268C>T		non_coding_transcript_exon_variant	3/3	4
ENSG00000267082	ENST00000588634.1 linkuse as main transcript	n.538-228G>A		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00783

AC:

1190

AN:

152016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00426

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00581

Gnomad FIN

AF:

0.0251

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0109

Gnomad OTH

AF:

0.00672

GnomAD3 exomes

AF:

0.00846

AC:

2109

AN:

249286

Hom.:

AF XY:

0.00861

AC XY:

1164

AN XY:

135248

show subpopulations

Gnomad AFR exome

AF:

0.000710

Gnomad AMR exome

AF:

0.00293

Gnomad ASJ exome

AF:

0.00209

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00761

Gnomad FIN exome

AF:

0.0237

Gnomad NFE exome

AF:

0.0106

Gnomad OTH exome

AF:

0.00578

GnomAD4 exome

AF:

0.00992

AC:

14496

AN:

1461610

Hom.:

Cov.:

AF XY:

0.00989

AC XY:

7190

AN XY:

727076

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.00291

Gnomad4 ASJ exome

AF:

0.00268

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00806

Gnomad4 FIN exome

AF:

0.0239

Gnomad4 NFE exome

AF:

0.0106

Gnomad4 OTH exome

AF:

0.00747

GnomAD4 genome

AF:

0.00782

AC:

1190

AN:

152134

Hom.:

Cov.:

AF XY:

0.00826

AC XY:

614

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00169

Gnomad4 AMR

AF:

0.00426

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00582

Gnomad4 FIN

AF:

0.0251

Gnomad4 NFE

AF:

0.0109

Gnomad4 OTH

AF:

0.00665

Alfa

AF:

0.00931

Hom.:

Bravo

AF:

0.00582

TwinsUK

AF:

0.0119

AC:

ALSPAC

AF:

0.0143

AC:

ESP6500AA

AF:

0.000520

AC:

ESP6500EA

AF:

0.00998

AC:

ExAC

AF:

0.00833

AC:

1007

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00834

EpiControl

AF:

0.00948

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:7

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Mar 10, 2017	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 19, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	DOCK6: BS1, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Adams-Oliver syndrome 2

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Nov 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.64

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

Eigen

Benign

0.032

Eigen_PC

Benign

0.021

FATHMM_MKL

Uncertain

0.90

LIST_S2

Pathogenic

1.0

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.8

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-5.8

REVEL

Benign

0.21

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

0.90

Vest4

0.93

MVP

0.37

MPC

0.81

ClinPred

0.054

GERP RS

2.5

Varity_R

0.56

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.28

Position offset: -11

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