Genetic Variant NM_001363540.2:c.465-77A>G (chr7-111984467-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001363540.2(DOCK4):c.465-77A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 1,268,878 control chromosomes in the GnomAD database, including 33,541 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.28 ( 7342 hom., cov: 32)

Exomes 𝑓: 0.20 ( 26199 hom. )

Consequence

DOCK4
NM_001363540.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.26

Publications

7 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK4	NM_001363540.2 link	c.465-77A>G		intron_variant	Intron 6 of 52	ENST00000428084.6	NP_001350469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK4	ENST00000428084.6 link	c.465-77A>G		intron_variant	Intron 6 of 52	5	NM_001363540.2	ENSP00000410746.1		Q8N1I0-3

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42762

AN:

151984

Hom.:

7318

Cov.:

show subpopulations

Gnomad AFR

AF:

0.489

Gnomad AMI

AF:

0.291

Gnomad AMR

AF:

0.202

Gnomad ASJ

AF:

0.232

Gnomad EAS

AF:

0.374

Gnomad SAS

AF:

0.217

Gnomad FIN

AF:

0.191

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.187

Gnomad OTH

AF:

0.262

GnomAD4 exome

AF:

0.204

AC:

228326

AN:

1116776

Hom.:

26199

AF XY:

0.204

AC XY:

114523

AN XY:

562598

show subpopulations

African (AFR)

AF:

0.504

AC:

12852

AN:

25492

American (AMR)

AF:

0.175

AC:

5744

AN:

32832

Ashkenazi Jewish (ASJ)

AF:

0.226

AC:

4933

AN:

21828

East Asian (EAS)

AF:

0.350

AC:

12084

AN:

34552

South Asian (SAS)

AF:

0.214

AC:

15072

AN:

70588

European-Finnish (FIN)

AF:

0.191

AC:

8998

AN:

47006

Middle Eastern (MID)

AF:

0.283

AC:

1429

AN:

5050

European-Non Finnish (NFE)

AF:

0.188

AC:

156193

AN:

831022

Other (OTH)

AF:

0.228

AC:

11021

AN:

48406

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

8510

17019

25529

34038

42548

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5146

10292

15438

20584

25730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.282

AC:

42822

AN:

152102

Hom.:

7342

Cov.:

AF XY:

0.279

AC XY:

20734

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.490

AC:

20295

AN:

41426

American (AMR)

AF:

0.201

AC:

3082

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.232

AC:

806

AN:

3470

East Asian (EAS)

AF:

0.374

AC:

1937

AN:

5180

South Asian (SAS)

AF:

0.216

AC:

1043

AN:

4824

European-Finnish (FIN)

AF:

0.191

AC:

2019

AN:

10586

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.187

AC:

12734

AN:

67998

Other (OTH)

AF:

0.261

AC:

551

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1455

2910

4364

5819

7274

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

414

828

1242

1656

2070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.193

Hom.:

1032

Bravo

AF:

0.296

Asia WGS

AF:

0.288

AC:

1005

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.0050

(source)

DANN

Benign

0.51

PhyloP100

-3.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over