Genetic Variant DOCK5:p.Pro1804Pro (chr8-25410106-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_024940.8(DOCK5):c.5412A>G(p.Pro1804Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 1,610,598 control chromosomes in the GnomAD database, including 305,203 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 0.53 ( 23361 hom., cov: 29)

Exomes 𝑓: 0.62 ( 281842 hom. )

Consequence

DOCK5
NM_024940.8 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.212

Publications

26 publications found

Variant links:

Genes affected

DOCK5 (HGNC:23476): (dedicator of cytokinesis 5) This gene encodes a member of the dedicator of cytokinesis protein family. Members of this family act as guanine nucleotide exchange factors for small Rho family G proteins. The protein encoded by this gene is thought to associate with adaptors CRK and CRKL, and function in regulation of intestinal epithelial cell spreading and migration on collagen IV. Similar proteins in mouse and zebrafish also function in myoblast fusion. [provided by RefSeq, Oct 2016]

DOCK5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP7

Synonymous conserved (PhyloP=-0.212 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK5	NM_024940.8 link	c.5412A>G	p.Pro1804Pro	synonymous_variant	Exon 51 of 52	ENST00000276440.12	NP_079216.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK5	ENST00000276440.12 link	c.5412A>G	p.Pro1804Pro	synonymous_variant	Exon 51 of 52	1	NM_024940.8	ENSP00000276440.7

Frequencies

GnomAD3 genomes

AF:

0.535

AC:

81044

AN:

151502

Hom.:

23357

Cov.:

show subpopulations

Gnomad AFR

AF:

0.295

Gnomad AMI

AF:

0.592

Gnomad AMR

AF:

0.600

Gnomad ASJ

AF:

0.637

Gnomad EAS

AF:

0.639

Gnomad SAS

AF:

0.594

Gnomad FIN

AF:

0.644

Gnomad MID

AF:

0.639

Gnomad NFE

AF:

0.630

Gnomad OTH

AF:

0.572

GnomAD2 exomes

AF:

0.599

AC:

149025

AN:

248840

AF XY:

0.604

show subpopulations

Gnomad AFR exome

AF:

0.290

Gnomad AMR exome

AF:

0.619

Gnomad ASJ exome

AF:

0.618

Gnomad EAS exome

AF:

0.619

Gnomad FIN exome

AF:

0.640

Gnomad NFE exome

AF:

0.621

Gnomad OTH exome

AF:

0.613

GnomAD4 exome

AF:

0.619

AC:

902628

AN:

1458976

Hom.:

281842

Cov.:

AF XY:

0.619

AC XY:

449593

AN XY:

725758

show subpopulations

African (AFR)

AF:

0.284

AC:

9511

AN:

33460

American (AMR)

AF:

0.615

AC:

27378

AN:

44514

Ashkenazi Jewish (ASJ)

AF:

0.622

AC:

16229

AN:

26088

East Asian (EAS)

AF:

0.639

AC:

25324

AN:

39634

South Asian (SAS)

AF:

0.608

AC:

52359

AN:

86052

European-Finnish (FIN)

AF:

0.636

AC:

33894

AN:

53318

Middle Eastern (MID)

AF:

0.601

AC:

3465

AN:

5768

European-Non Finnish (NFE)

AF:

0.629

AC:

697659

AN:

1109880

Other (OTH)

AF:

0.611

AC:

36809

AN:

60262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

15148

30297

45445

60594

75742

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18540

37080

55620

74160

92700

<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:

0.535

AC:

81070

AN:

151622

Hom.:

23361

Cov.:

AF XY:

0.539

AC XY:

39910

AN XY:

74006

show subpopulations

African (AFR)

AF:

0.295

AC:

12185

AN:

41332

American (AMR)

AF:

0.600

AC:

9140

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.637

AC:

2208

AN:

3468

East Asian (EAS)

AF:

0.639

AC:

3228

AN:

5054

South Asian (SAS)

AF:

0.595

AC:

2861

AN:

4812

European-Finnish (FIN)

AF:

0.644

AC:

6753

AN:

10488

Middle Eastern (MID)

AF:

0.642

AC:

185

AN:

288

European-Non Finnish (NFE)

AF:

0.630

AC:

42770

AN:

67924

Other (OTH)

AF:

0.570

AC:

1200

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1732

3465

5197

6930

8662

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

704

1408

2112

2816

3520

<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:

0.600

Hom.:

40789

Bravo

AF:

0.520

Asia WGS

AF:

0.573

AC:

1994

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.37

(source)

DANN

Benign

0.51

PhyloP100

-0.21

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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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