dbSNP rs2296990: DOCK9:c.4013+41C>T (chr13-98850006-G-A) – 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.4013+41C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0588 in 1,415,940 control chromosomes in the GnomAD database, including 3,695 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 0.051 ( 341 hom., cov: 32)

Exomes 𝑓: 0.060 ( 3354 hom. )

Consequence

DOCK9
NM_001366683.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.601

Publications

4 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=-0.72).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK9	NM_001366683.2 link	c.4013+41C>T		intron_variant	Intron 36 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.4013+41C>T		intron_variant	Intron 36 of 52		NM_001366683.2	ENSP00000507034.1		A0A804HIE8

Frequencies

GnomAD3 genomes

AF:

0.0515

AC:

7822

AN:

151994

Hom.:

339

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0156

Gnomad AMI

AF:

0.0954

Gnomad AMR

AF:

0.0915

Gnomad ASJ

AF:

0.0591

Gnomad EAS

AF:

0.184

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.0413

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0496

Gnomad OTH

AF:

0.0688

GnomAD2 exomes

AF:

0.0820

AC:

13162

AN:

160464

AF XY:

0.0798

show subpopulations

Gnomad AFR exome

AF:

0.0152

Gnomad AMR exome

AF:

0.167

Gnomad ASJ exome

AF:

0.0639

Gnomad EAS exome

AF:

0.179

Gnomad FIN exome

AF:

0.0414

Gnomad NFE exome

AF:

0.0504

Gnomad OTH exome

AF:

0.0721

GnomAD4 exome

AF:

0.0597

AC:

75417

AN:

1263826

Hom.:

3354

Cov.:

AF XY:

0.0607

AC XY:

38257

AN XY:

630180

show subpopulations

African (AFR)

AF:

0.0141

AC:

405

AN:

28818

American (AMR)

AF:

0.154

AC:

5340

AN:

34586

Ashkenazi Jewish (ASJ)

AF:

0.0665

AC:

1614

AN:

24280

East Asian (EAS)

AF:

0.238

AC:

8507

AN:

35790

South Asian (SAS)

AF:

0.103

AC:

7759

AN:

75454

European-Finnish (FIN)

AF:

0.0406

AC:

2004

AN:

49410

Middle Eastern (MID)

AF:

0.0974

AC:

525

AN:

5388

European-Non Finnish (NFE)

AF:

0.0481

AC:

45964

AN:

956564

Other (OTH)

AF:

0.0616

AC:

3299

AN:

53536

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

3040

6080

9121

12161

15201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1770

3540

5310

7080

8850

<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:

0.0514

AC:

7826

AN:

152114

Hom.:

341

Cov.:

AF XY:

0.0540

AC XY:

4018

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.0156

AC:

647

AN:

41496

American (AMR)

AF:

0.0917

AC:

1403

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0591

AC:

205

AN:

3468

East Asian (EAS)

AF:

0.184

AC:

950

AN:

5176

South Asian (SAS)

AF:

0.116

AC:

560

AN:

4816

European-Finnish (FIN)

AF:

0.0413

AC:

437

AN:

10574

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0496

AC:

3370

AN:

67970

Other (OTH)

AF:

0.0691

AC:

146

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

368

736

1105

1473

1841

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<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:

0.0526

Hom.:

192

Bravo

AF:

0.0581

Asia WGS

AF:

0.148

AC:

514

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

7.6

(source)

DANN

Benign

0.70

PhyloP100

0.60

PromoterAI

-0.0049

Neutral

(source)

Mutation Taster

=21/79

disease causing

(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