Variant rs869801 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001290223.2(DOCK1):c.5440G>A(p.Ala1814Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,612,100 control chromosomes in the GnomAD database, including 53,328 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 4657 hom., cov: 33)

Exomes 𝑓: 0.25 ( 48671 hom. )

Consequence

DOCK1
NM_001290223.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.848

Variant links:

Genes affected

DOCK1 (HGNC:2987): (dedicator of cytokinesis 1) This gene encodes a member of the dedicator of cytokinesis protein family. Dedicator of cytokinesis proteins act as guanine nucleotide exchange factors for small Rho family G proteins. The encoded protein regulates the small GTPase Rac, thereby influencing several biological processes, including phagocytosis and cell migration. Overexpression of this gene has also been associated with certain cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

DOCK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003914416).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK1	NM_001290223.2 linkuse as main transcript	c.5440G>A	p.Ala1814Thr	missense_variant	51/52	ENST00000623213.2	NP_001277152.2	B2RUU3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK1	ENST00000623213.2 linkuse as main transcript	c.5440G>A	p.Ala1814Thr	missense_variant	51/52	1	NM_001290223.2	ENSP00000485033.1		A0A096LNH6
DOCK1	ENST00000280333.9 linkuse as main transcript	c.5377G>A	p.Ala1793Thr	missense_variant	51/52	1		ENSP00000280333.6		Q14185

Frequencies

GnomAD3 genomes

AF:

0.242

AC:

36839

AN:

152002

Hom.:

4648

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.249

Gnomad AMR

AF:

0.249

Gnomad ASJ

AF:

0.320

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.240

Gnomad FIN

AF:

0.232

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.264

Gnomad OTH

AF:

0.247

GnomAD3 exomes

AF:

0.236

AC:

57962

AN:

245332

Hom.:

7141

AF XY:

0.241

AC XY:

32017

AN XY:

133050

show subpopulations

Gnomad AFR exome

AF:

0.213

Gnomad AMR exome

AF:

0.196

Gnomad ASJ exome

AF:

0.332

Gnomad EAS exome

AF:

0.122

Gnomad SAS exome

AF:

0.242

Gnomad FIN exome

AF:

0.234

Gnomad NFE exome

AF:

0.260

Gnomad OTH exome

AF:

0.247

GnomAD4 exome

AF:

0.255

AC:

372054

AN:

1459980

Hom.:

48671

Cov.:

AF XY:

0.256

AC XY:

186060

AN XY:

726018

show subpopulations

Gnomad4 AFR exome

AF:

0.217

Gnomad4 AMR exome

AF:

0.204

Gnomad4 ASJ exome

AF:

0.338

Gnomad4 EAS exome

AF:

0.114

Gnomad4 SAS exome

AF:

0.247

Gnomad4 FIN exome

AF:

0.234

Gnomad4 NFE exome

AF:

0.262

Gnomad4 OTH exome

AF:

0.261

GnomAD4 genome

AF:

0.242

AC:

36868

AN:

152120

Hom.:

4657

Cov.:

AF XY:

0.241

AC XY:

17941

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.216

Gnomad4 AMR

AF:

0.248

Gnomad4 ASJ

AF:

0.320

Gnomad4 EAS

AF:

0.118

Gnomad4 SAS

AF:

0.241

Gnomad4 FIN

AF:

0.232

Gnomad4 NFE

AF:

0.264

Gnomad4 OTH

AF:

0.245

Alfa

AF:

0.259

Hom.:

11008

Bravo

AF:

0.240

TwinsUK

AF:

0.266

AC:

987

ALSPAC

AF:

0.267

AC:

1030

ESP6500AA

AF:

0.193

AC:

769

ESP6500EA

AF:

0.259

AC:

2153

ExAC

AF:

0.234

AC:

28235

Asia WGS

AF:

0.189

AC:

661

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.36

DANN

Benign

0.87

DEOGEN2

Benign

0.071

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.53

T;T

MetaRNN

Benign

0.0039

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.0

L;.

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.27

N;.

REVEL

Benign

0.078

Sift

Benign

0.70

T;.

Sift4G

Benign

0.50

T;T

Polyphen

0.0

B;.

Vest4

0.027

MPC

0.23

ClinPred

0.015

GERP RS

-10

Varity_R

0.031

gMVP

0.055

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over