dbSNP rs7995432: DOCK9:c.717+43A>G (chr13-98920911-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_001366683.2(DOCK9):c.717+43A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0435 in 1,546,418 control chromosomes in the GnomAD database, including 2,140 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 0.069 ( 594 hom., cov: 33)

Exomes 𝑓: 0.041 ( 1546 hom. )

Consequence

DOCK9
NM_001366683.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0360

Publications

6 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 Gene-Disease associations (from GenCC):

keratoconus
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

DOCK9 links:

Genome browser will be placed here

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=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK9	NM_001366683.2 link	c.717+43A>G		intron_variant	Intron 7 of 52	ENST00000682017.1	NP_001353612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK9	ENST00000682017.1 link	c.717+43A>G		intron_variant	Intron 7 of 52		NM_001366683.2	ENSP00000507034.1		A0A804HIE8

Frequencies

GnomAD3 genomes

AF:

0.0689

AC:

10489

AN:

152190

Hom.:

594

Cov.:

show subpopulations

Gnomad AFR

AF:

0.157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0424

Gnomad ASJ

AF:

0.0259

Gnomad EAS

AF:

0.0469

Gnomad SAS

AF:

0.0634

Gnomad FIN

AF:

0.0172

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0347

Gnomad OTH

AF:

0.0621

GnomAD2 exomes

AF:

0.0432

AC:

8085

AN:

187266

AF XY:

0.0434

show subpopulations

Gnomad AFR exome

AF:

0.156

Gnomad AMR exome

AF:

0.0238

Gnomad ASJ exome

AF:

0.0251

Gnomad EAS exome

AF:

0.0346

Gnomad FIN exome

AF:

0.0178

Gnomad NFE exome

AF:

0.0341

Gnomad OTH exome

AF:

0.0355

GnomAD4 exome

AF:

0.0407

AC:

56777

AN:

1394110

Hom.:

1546

Cov.:

AF XY:

0.0411

AC XY:

28304

AN XY:

688664

show subpopulations

African (AFR)

AF:

0.157

AC:

4874

AN:

31086

American (AMR)

AF:

0.0253

AC:

836

AN:

33048

Ashkenazi Jewish (ASJ)

AF:

0.0252

AC:

595

AN:

23628

East Asian (EAS)

AF:

0.0807

AC:

3123

AN:

38718

South Asian (SAS)

AF:

0.0659

AC:

5008

AN:

76008

European-Finnish (FIN)

AF:

0.0180

AC:

900

AN:

50008

Middle Eastern (MID)

AF:

0.0370

AC:

183

AN:

4944

European-Non Finnish (NFE)

AF:

0.0358

AC:

38640

AN:

1079064

Other (OTH)

AF:

0.0454

AC:

2618

AN:

57606

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

2333

4667

7000

9334

11667

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1604

3208

4812

6416

8020

<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:

0.0690

AC:

10504

AN:

152308

Hom.:

594

Cov.:

AF XY:

0.0680

AC XY:

5066

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.157

AC:

6530

AN:

41538

American (AMR)

AF:

0.0424

AC:

648

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0259

AC:

AN:

3470

East Asian (EAS)

AF:

0.0470

AC:

244

AN:

5194

South Asian (SAS)

AF:

0.0634

AC:

306

AN:

4826

European-Finnish (FIN)

AF:

0.0172

AC:

183

AN:

10622

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0347

AC:

2360

AN:

68036

Other (OTH)

AF:

0.0614

AC:

130

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

481

963

1444

1926

2407

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<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:

0.0446

Hom.:

348

Bravo

AF:

0.0732

Asia WGS

AF:

0.0590

AC:

206

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.71

(source)

DANN

Benign

0.81

PhyloP100

-0.036

Mutation Taster

=100/0

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