Genetic Variant NM_001366683.2:c.474C>T (chr13-98923314-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

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

The NM_001366683.2(DOCK9):c.474C>T(p.Val158Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 1,612,214 control chromosomes in the GnomAD database, including 23,051 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 0.15 ( 1851 hom., cov: 33)

Exomes 𝑓: 0.17 ( 21200 hom. )

Consequence

DOCK9
NM_001366683.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.571

Publications

18 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP7

Synonymous conserved (PhyloP=-0.571 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK9	NM_001366683.2 link	c.474C>T	p.Val158Val	synonymous_variant	Exon 5 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.474C>T	p.Val158Val	synonymous_variant	Exon 5 of 53		NM_001366683.2	ENSP00000507034.1		A0A804HIE8

Frequencies

GnomAD3 genomes

AF:

0.149

AC:

22616

AN:

152032

Hom.:

1850

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0890

Gnomad AMI

AF:

0.160

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.171

Gnomad EAS

AF:

0.194

Gnomad SAS

AF:

0.212

Gnomad FIN

AF:

0.157

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.171

Gnomad OTH

AF:

0.173

GnomAD2 exomes

AF:

0.181

AC:

45108

AN:

248996

AF XY:

0.181

show subpopulations

Gnomad AFR exome

AF:

0.0883

Gnomad AMR exome

AF:

0.236

Gnomad ASJ exome

AF:

0.174

Gnomad EAS exome

AF:

0.199

Gnomad FIN exome

AF:

0.164

Gnomad NFE exome

AF:

0.172

Gnomad OTH exome

AF:

0.170

GnomAD4 exome

AF:

0.167

AC:

244533

AN:

1460064

Hom.:

21200

Cov.:

AF XY:

0.169

AC XY:

122546

AN XY:

726410

show subpopulations

African (AFR)

AF:

0.0849

AC:

2840

AN:

33462

American (AMR)

AF:

0.225

AC:

10055

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

4527

AN:

26122

East Asian (EAS)

AF:

0.242

AC:

9618

AN:

39674

South Asian (SAS)

AF:

0.204

AC:

17593

AN:

86152

European-Finnish (FIN)

AF:

0.167

AC:

8896

AN:

53376

Middle Eastern (MID)

AF:

0.199

AC:

1143

AN:

5758

European-Non Finnish (NFE)

AF:

0.162

AC:

179809

AN:

1110528

Other (OTH)

AF:

0.167

AC:

10052

AN:

60306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

9821

19642

29463

39284

49105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6330

12660

18990

25320

31650

<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:

0.149

AC:

22633

AN:

152150

Hom.:

1851

Cov.:

AF XY:

0.149

AC XY:

11115

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.0893

AC:

3706

AN:

41506

American (AMR)

AF:

0.161

AC:

2453

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.171

AC:

593

AN:

3468

East Asian (EAS)

AF:

0.194

AC:

1006

AN:

5182

South Asian (SAS)

AF:

0.212

AC:

1021

AN:

4824

European-Finnish (FIN)

AF:

0.157

AC:

1664

AN:

10584

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.171

AC:

11621

AN:

67988

Other (OTH)

AF:

0.172

AC:

364

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

985

1970

2955

3940

4925

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

256

512

768

1024

1280

<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:

0.145

Hom.:

943

Bravo

AF:

0.148

EpiCase

AF:

0.173

EpiControl

AF:

0.170

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

2.9

(source)

DANN

Benign

0.68

PhyloP100

-0.57

Mutation Taster

=86/14

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