Variant 7-111728425-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001363540.2(DOCK4):c.5777C>T(p.Pro1926Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00512 in 1,584,366 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0033 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0053 ( 29 hom. )

Consequence

DOCK4
NM_001363540.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.33

Variant links:

Genes affected

DOCK4 (HGNC:19192): (dedicator of cytokinesis 4) This gene is a member of the dedicator of cytokinesis (DOCK) family and encodes a protein with a DHR-1 (CZH-1) domain, a DHR-2 (CZH-2) domain and an SH3 domain. This membrane-associated, cytoplasmic protein functions as a guanine nucleotide exchange factor and is involved in regulation of adherens junctions between cells. Mutations in this gene have been associated with ovarian, prostate, glioma, and colorectal cancers. Alternatively spliced variants which encode different protein isoforms have been described, but only one has been fully characterized. [provided by RefSeq, Jul 2008]

DOCK4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0074597597).

BP6

Variant 7-111728425-G-A is Benign according to our data. Variant chr7-111728425-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 719177.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 501 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK4	NM_001363540.2 linkuse as main transcript	c.5777C>T	p.Pro1926Leu	missense_variant	53/53	ENST00000428084.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK4	ENST00000428084.6 linkuse as main transcript	c.5777C>T	p.Pro1926Leu	missense_variant	53/53	5	NM_001363540.2	P3	Q8N1I0-3

Frequencies

GnomAD3 genomes

AF:

0.00329

AC:

501

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00594

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00292

AC:

649

AN:

222232

Hom.:

AF XY:

0.00300

AC XY:

360

AN XY:

120004

show subpopulations

Gnomad AFR exome

AF:

0.000837

Gnomad AMR exome

AF:

0.00191

Gnomad ASJ exome

AF:

0.000133

Gnomad EAS exome

AF:

0.0000567

Gnomad SAS exome

AF:

0.000314

Gnomad FIN exome

AF:

0.00154

Gnomad NFE exome

AF:

0.00522

Gnomad OTH exome

AF:

0.00277

GnomAD4 exome

AF:

0.00531

AC:

7605

AN:

1432018

Hom.:

Cov.:

AF XY:

0.00525

AC XY:

3721

AN XY:

708350

show subpopulations

Gnomad4 AFR exome

AF:

0.000784

Gnomad4 AMR exome

AF:

0.00162

Gnomad4 ASJ exome

AF:

0.000126

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000283

Gnomad4 FIN exome

AF:

0.00181

Gnomad4 NFE exome

AF:

0.00652

Gnomad4 OTH exome

AF:

0.00396

GnomAD4 genome

AF:

0.00329

AC:

501

AN:

152348

Hom.:

Cov.:

AF XY:

0.00322

AC XY:

240

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000769

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.00594

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00408

Hom.:

Bravo

AF:

0.00327

TwinsUK

AF:

0.00755

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.000756

AC:

ESP6500EA

AF:

0.00572

AC:

ExAC

AF:

0.00316

AC:

380

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.66

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.15

Cadd

Pathogenic

Dann

Pathogenic

1.0

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Benign

0.047

MetaRNN

Benign

0.0075

T;T

MetaSVM

Benign

-0.87

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-2.3

N;N

REVEL

Benign

0.21

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.014

D;D

Polyphen

1.0

.;D

Vest4

0.29

MVP

0.41

MPC

0.34

ClinPred

0.023

GERP RS

5.6

Varity_R

0.22

gMVP

0.35

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