NM_001367561.1:c.541A>G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001367561.1(DOCK7):c.541A>G(p.Met181Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,611,734 control chromosomes in the GnomAD database, including 908 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M181L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.039 ( 346 hom., cov: 32)

Exomes 𝑓: 0.0074 ( 562 hom. )

Consequence

DOCK7
NM_001367561.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.29

Variant links:

Genes affected

DOCK7 (HGNC:19190): (dedicator of cytokinesis 7) The protein encoded by this gene is a guanine nucleotide exchange factor (GEF) that plays a role in axon formation and neuronal polarization. The encoded protein displays GEF activity toward RAC1 and RAC3 Rho small GTPases but not toward CDC42. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

DOCK7 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=0.0019033551).

BP6

Variant 1-62648297-T-C is Benign according to our data. Variant chr1-62648297-T-C is described in ClinVar as [Benign]. Clinvar id is 447277.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK7	NM_001367561.1 link	c.541A>G	p.Met181Val	missense_variant	Exon 6 of 50	ENST00000635253.2	NP_001354490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK7	ENST00000635253.2 link	c.541A>G	p.Met181Val	missense_variant	Exon 6 of 50	5	NM_001367561.1	ENSP00000489124.1		Q96N67-1

Frequencies

GnomAD3 genomes

AF:

0.0385

AC:

5861

AN:

152076

Hom.:

347

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0132

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.122

Gnomad SAS

AF:

0.00765

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.0297

GnomAD3 exomes

AF:

0.0183

AC:

4566

AN:

249086

Hom.:

266

AF XY:

0.0154

AC XY:

2088

AN XY:

135190

show subpopulations

Gnomad AFR exome

AF:

0.120

Gnomad AMR exome

AF:

0.00473

Gnomad ASJ exome

AF:

0.00340

Gnomad EAS exome

AF:

0.120

Gnomad SAS exome

AF:

0.00511

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000826

Gnomad OTH exome

AF:

0.00827

GnomAD4 exome

AF:

0.00741

AC:

10814

AN:

1459540

Hom.:

562

Cov.:

AF XY:

0.00695

AC XY:

5047

AN XY:

726046

show subpopulations

Gnomad4 AFR exome

AF:

0.117

Gnomad4 AMR exome

AF:

0.00569

Gnomad4 ASJ exome

AF:

0.00315

Gnomad4 EAS exome

AF:

0.121

Gnomad4 SAS exome

AF:

0.00519

Gnomad4 FIN exome

AF:

0.0000751

Gnomad4 NFE exome

AF:

0.000456

Gnomad4 OTH exome

AF:

0.0129

GnomAD4 genome

AF:

0.0385

AC:

5862

AN:

152194

Hom.:

346

Cov.:

AF XY:

0.0384

AC XY:

2856

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.118

Gnomad4 AMR

AF:

0.0132

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.121

Gnomad4 SAS

AF:

0.00766

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000603

Gnomad4 OTH

AF:

0.0294

Alfa

AF:

0.00846

Hom.:

Bravo

AF:

0.0438

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.110

AC:

484

ESP6500EA

AF:

0.000931

AC:

ExAC

AF:

0.0208

AC:

2525

Asia WGS

AF:

0.0540

AC:

188

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy, 23

Benign:2

Apr 11, 2023

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Mar 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Jun 29, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.084

.;.;.;.;.;T;.

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.52

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.62

T;T;T;T;T;T;T

MetaRNN

Benign

0.0019

T;T;T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-1.1

N;N;N;N;N;N;N

PrimateAI

Uncertain

0.59

PROVEAN

Benign

0.24

N;.;N;.;.;.;N

REVEL

Benign

0.14

Sift

Benign

0.71

T;.;T;.;.;.;T

Sift4G

Benign

0.66

T;T;T;T;T;T;T

Polyphen

0.0, 0.0010

.;B;B;B;B;.;.

Vest4

0.095

MPC

0.39

ClinPred

0.00074

GERP RS

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.28

gMVP

0.41

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