rs62620184

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001366683.2(DOCK9):c.1301C>T(p.Ala434Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0437 in 1,613,954 control chromosomes in the GnomAD database, including 1,873 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 136 hom., cov: 33)

Exomes 𝑓: 0.045 ( 1737 hom. )

Consequence

DOCK9
NM_001366683.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.62

Publications

9 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022068322).

BP6

Variant 13-98902367-G-A is Benign according to our data. Variant chr13-98902367-G-A is described in CliVar as Benign. Clinvar id is 402794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-98902367-G-A is described in CliVar as Benign. Clinvar id is 402794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-98902367-G-A is described in CliVar as Benign. Clinvar id is 402794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-98902367-G-A is described in CliVar as Benign. Clinvar id is 402794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-98902367-G-A is described in CliVar as Benign. Clinvar id is 402794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-98902367-G-A is described in CliVar as Benign. Clinvar id is 402794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-98902367-G-A is described in CliVar as Benign. Clinvar id is 402794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-98902367-G-A is described in CliVar as Benign. Clinvar id is 402794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-98902367-G-A is described in CliVar as Benign. Clinvar id is 402794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-98902367-G-A is described in CliVar as Benign. Clinvar id is 402794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-98902367-G-A is described in CliVar as Benign. Clinvar id is 402794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-98902367-G-A is described in CliVar as Benign. Clinvar id is 402794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-98902367-G-A is described in CliVar as Benign. Clinvar id is 402794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-98902367-G-A is described in CliVar as Benign. Clinvar id is 402794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-98902367-G-A is described in CliVar as Benign. Clinvar id is 402794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-98902367-G-A is described in CliVar as Benign. Clinvar id is 402794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-98902367-G-A is described in CliVar as Benign. Clinvar id is 402794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-98902367-G-A is described in CliVar as Benign. Clinvar id is 402794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-98902367-G-A is described in CliVar as Benign. Clinvar id is 402794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-98902367-G-A is described in CliVar as Benign. Clinvar id is 402794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-98902367-G-A is described in CliVar as Benign. Clinvar id is 402794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-98902367-G-A is described in CliVar as Benign. Clinvar id is 402794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-98902367-G-A is described in CliVar as Benign. Clinvar id is 402794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-98902367-G-A is described in CliVar as Benign. Clinvar id is 402794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-98902367-G-A is described in CliVar as Benign. Clinvar id is 402794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-98902367-G-A is described in CliVar as Benign. Clinvar id is 402794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-98902367-G-A is described in CliVar as Benign. Clinvar id is 402794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-98902367-G-A is described in CliVar as Benign. Clinvar id is 402794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK9	NM_001366683.2 link	c.1301C>T	p.Ala434Val	missense_variant	Exon 12 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.1301C>T	p.Ala434Val	missense_variant	Exon 12 of 53		NM_001366683.2	ENSP00000507034.1		A0A804HIE8

Frequencies

GnomAD3 genomes

AF:

0.0336

AC:

5109

AN:

152186

Hom.:

135

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00866

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.0361

Gnomad ASJ

AF:

0.0533

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0830

Gnomad FIN

AF:

0.0400

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0446

Gnomad OTH

AF:

0.0344

GnomAD2 exomes

AF:

0.0432

AC:

10763

AN:

249154

AF XY:

0.0468

show subpopulations

Gnomad AFR exome

AF:

0.00684

Gnomad AMR exome

AF:

0.0262

Gnomad ASJ exome

AF:

0.0512

Gnomad EAS exome

AF:

0.000835

Gnomad FIN exome

AF:

0.0395

Gnomad NFE exome

AF:

0.0473

Gnomad OTH exome

AF:

0.0481

GnomAD4 exome

AF:

0.0448

AC:

65431

AN:

1461650

Hom.:

1737

Cov.:

AF XY:

0.0463

AC XY:

33647

AN XY:

727116

show subpopulations

African (AFR)

AF:

0.00857

AC:

287

AN:

33480

American (AMR)

AF:

0.0264

AC:

1182

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0534

AC:

1396

AN:

26136

East Asian (EAS)

AF:

0.000453

AC:

AN:

39696

South Asian (SAS)

AF:

0.0868

AC:

7487

AN:

86256

European-Finnish (FIN)

AF:

0.0391

AC:

2087

AN:

53386

Middle Eastern (MID)

AF:

0.0860

AC:

496

AN:

5768

European-Non Finnish (NFE)

AF:

0.0447

AC:

49719

AN:

1111836

Other (OTH)

AF:

0.0457

AC:

2759

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

3552

7104

10656

14208

17760

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1884

3768

5652

7536

9420

<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:

0.0336

AC:

5110

AN:

152304

Hom.:

136

Cov.:

AF XY:

0.0340

AC XY:

2535

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00866

AC:

360

AN:

41564

American (AMR)

AF:

0.0360

AC:

551

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0533

AC:

185

AN:

3470

East Asian (EAS)

AF:

0.00135

AC:

AN:

5184

South Asian (SAS)

AF:

0.0836

AC:

403

AN:

4818

European-Finnish (FIN)

AF:

0.0400

AC:

425

AN:

10616

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0446

AC:

3035

AN:

68032

Other (OTH)

AF:

0.0327

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

269

538

808

1077

1346

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<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:

0.0407

Hom.:

484

Bravo

AF:

0.0308

TwinsUK

AF:

0.0464

AC:

172

ALSPAC

AF:

0.0423

AC:

163

ESP6500AA

AF:

0.00869

AC:

ESP6500EA

AF:

0.0455

AC:

386

ExAC

AF:

0.0447

AC:

5411

Asia WGS

AF:

0.0370

AC:

129

AN:

3478

EpiCase

AF:

0.0465

EpiControl

AF:

0.0479

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.028

.;.;.;.;T

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.85

D;D;D;D;D

MetaRNN

Benign

0.0022

T;T;T;T;T

MetaSVM

Benign

-1.1

PhyloP100

1.6

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.1

N;N;N;.;.

REVEL

Benign

0.035

Sift

Benign

0.14

T;T;T;.;.

Sift4G

Benign

0.25

.;T;T;T;T

Polyphen

0.0

.;B;.;.;.

Vest4

0.11, 0.082, 0.14, 0.13

MPC

0.30

ClinPred

0.0030

GERP RS

0.31

gMVP

0.12

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over