dbSNP rs17709314: DOCK9:p.Ala1656Ala (chr13-98826885-T-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_001366683.2(DOCK9):c.4968A>G(p.Ala1656Ala) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,605,618 control chromosomes in the GnomAD database, including 9,619 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.077 ( 571 hom., cov: 33)

Exomes 𝑓: 0.11 ( 9048 hom. )

Consequence

DOCK9
NM_001366683.2 splice_region, synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.687

Publications

14 publications found

Variant links:

Genes affected

DOCK9 (HGNC:14132): (dedicator of cytokinesis 9) Enables cadherin binding activity. Predicted to be involved in positive regulation of GTPase activity. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

DOCK9 links:

DOCK9-AS1 (HGNC:40672): (DOCK9 antisense RNA 1)

DOCK9-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.038).

BP7

Synonymous conserved (PhyloP=-0.687 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK9	NM_001366683.2 link	c.4968A>G	p.Ala1656Ala	splice_region_variant, synonymous_variant	Exon 44 of 53	ENST00000682017.1	NP_001353612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK9	ENST00000682017.1 link	c.4968A>G	p.Ala1656Ala	splice_region_variant, synonymous_variant	Exon 44 of 53		NM_001366683.2	ENSP00000507034.1		A0A804HIE8

Frequencies

GnomAD3 genomes

AF:

0.0767

AC:

11673

AN:

152202

Hom.:

570

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0218

Gnomad AMI

AF:

0.0800

Gnomad AMR

AF:

0.0683

Gnomad ASJ

AF:

0.0790

Gnomad EAS

AF:

0.000960

Gnomad SAS

AF:

0.0553

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.0789

GnomAD2 exomes

AF:

0.0799

AC:

19302

AN:

241662

AF XY:

0.0815

show subpopulations

Gnomad AFR exome

AF:

0.0209

Gnomad AMR exome

AF:

0.0408

Gnomad ASJ exome

AF:

0.0753

Gnomad EAS exome

AF:

0.000398

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.112

Gnomad OTH exome

AF:

0.0876

GnomAD4 exome

AF:

0.106

AC:

153632

AN:

1453298

Hom.:

9048

Cov.:

AF XY:

0.105

AC XY:

75646

AN XY:

722552

show subpopulations

African (AFR)

AF:

0.0194

AC:

649

AN:

33436

American (AMR)

AF:

0.0436

AC:

1924

AN:

44080

Ashkenazi Jewish (ASJ)

AF:

0.0778

AC:

2027

AN:

26038

East Asian (EAS)

AF:

0.000404

AC:

AN:

39626

South Asian (SAS)

AF:

0.0589

AC:

4991

AN:

84776

European-Finnish (FIN)

AF:

0.118

AC:

6291

AN:

53214

Middle Eastern (MID)

AF:

0.0498

AC:

287

AN:

5758

European-Non Finnish (NFE)

AF:

0.119

AC:

131673

AN:

1106236

Other (OTH)

AF:

0.0960

AC:

5774

AN:

60134

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

5740

11480

17221

22961

28701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4672

9344

14016

18688

23360

<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:

0.0766

AC:

11675

AN:

152320

Hom.:

571

Cov.:

AF XY:

0.0750

AC XY:

5584

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0217

AC:

904

AN:

41578

American (AMR)

AF:

0.0682

AC:

1043

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0790

AC:

274

AN:

3470

East Asian (EAS)

AF:

0.000963

AC:

AN:

5194

South Asian (SAS)

AF:

0.0556

AC:

268

AN:

4822

European-Finnish (FIN)

AF:

0.110

AC:

1164

AN:

10614

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.114

AC:

7768

AN:

68018

Other (OTH)

AF:

0.0781

AC:

165

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

548

1097

1645

2194

2742

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<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:

0.0969

Hom.:

1432

Bravo

AF:

0.0706

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

4.2

(source)

DANN

Benign

0.71

PhyloP100

-0.69

Mutation Taster

=89/11

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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