Variant 10-126981957-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong

The NM_001290223.2(DOCK1):c.211A>G(p.Ile71Val) variant causes a missense change. The variant allele was found at a frequency of 0.000778 in 1,613,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00081 ( 0 hom. )

Consequence

DOCK1
NM_001290223.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.49

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 Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, DOCK1

BP4

Computational evidence support a benign effect (MetaRNN=0.028178483).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK1	NM_001290223.2 linkuse as main transcript	c.211A>G	p.Ile71Val	missense_variant	4/52	ENST00000623213.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK1	ENST00000623213.2 linkuse as main transcript	c.211A>G	p.Ile71Val	missense_variant	4/52	1	NM_001290223.2
DOCK1	ENST00000280333.9 linkuse as main transcript	c.211A>G	p.Ile71Val	missense_variant	4/52	1		P1

Frequencies

GnomAD3 genomes

AF:

0.000487

AC:

AN:

151970

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000339

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000868

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000486

AC:

121

AN:

248910

Hom.:

AF XY:

0.000533

AC XY:

AN XY:

135056

show subpopulations

Gnomad AFR exome

AF:

0.000258

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000930

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000809

AC:

1182

AN:

1461472

Hom.:

Cov.:

AF XY:

0.000838

AC XY:

609

AN XY:

727002

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.00102

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.000487

AC:

AN:

151970

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.000339

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000945

Gnomad4 NFE

AF:

0.000868

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000587

Hom.:

Bravo

AF:

0.000453

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000541

AC:

ESP6500EA

AF:

0.000489

AC:

ExAC

AF:

0.000637

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 03, 2023

The c.211A>G (p.I71V) alteration is located in exon 4 (coding exon 4) of the DOCK1 gene. This alteration results from a A to G substitution at nucleotide position 211, causing the isoleucine (I) at amino acid position 71 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.71

Cadd

Benign

Dann

Benign

0.85

DEOGEN2

Benign

0.060

T;T

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.30

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.64

T;T

M_CAP

Benign

0.0022

MetaRNN

Benign

0.028

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.76

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.44

PROVEAN

Benign

0.14

N;.

REVEL

Benign

0.10

Sift

Benign

0.65

T;.

Sift4G

Benign

0.72

T;T

Polyphen

0.0

B;.

Vest4

0.23

MVP

0.54

MPC

0.20

ClinPred

0.020

GERP RS

4.9

Varity_R

0.089

gMVP

0.22

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