Genetic Variant NM_001366683.2:c.2043+18A>G (chr13-98888140-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.2043+18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,534,712 control chromosomes in the GnomAD database, including 15,514 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 0.13 ( 1324 hom., cov: 32)

Exomes 𝑓: 0.14 ( 14190 hom. )

Consequence

DOCK9
NM_001366683.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.50

Publications

5 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=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK9	NM_001366683.2 link	c.2043+18A>G		intron_variant	Intron 18 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.2043+18A>G		intron_variant	Intron 18 of 52		NM_001366683.2	ENSP00000507034.1		A0A804HIE8

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19226

AN:

152048

Hom.:

1321

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0769

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.145

Gnomad ASJ

AF:

0.149

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.203

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.201

Gnomad NFE

AF:

0.141

Gnomad OTH

AF:

0.151

GnomAD2 exomes

AF:

0.156

AC:

30768

AN:

197014

AF XY:

0.155

show subpopulations

Gnomad AFR exome

AF:

0.0752

Gnomad AMR exome

AF:

0.217

Gnomad ASJ exome

AF:

0.154

Gnomad EAS exome

AF:

0.204

Gnomad FIN exome

AF:

0.120

Gnomad NFE exome

AF:

0.140

Gnomad OTH exome

AF:

0.149

GnomAD4 exome

AF:

0.139

AC:

191688

AN:

1382544

Hom.:

14190

Cov.:

AF XY:

0.141

AC XY:

96695

AN XY:

687012

show subpopulations

African (AFR)

AF:

0.0724

AC:

2242

AN:

30952

American (AMR)

AF:

0.206

AC:

7383

AN:

35854

Ashkenazi Jewish (ASJ)

AF:

0.153

AC:

3777

AN:

24724

East Asian (EAS)

AF:

0.242

AC:

9411

AN:

38854

South Asian (SAS)

AF:

0.195

AC:

15140

AN:

77650

European-Finnish (FIN)

AF:

0.124

AC:

6364

AN:

51210

Middle Eastern (MID)

AF:

0.193

AC:

1043

AN:

5392

European-Non Finnish (NFE)

AF:

0.130

AC:

138259

AN:

1060308

Other (OTH)

AF:

0.140

AC:

8069

AN:

57600

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

7302

14604

21907

29209

36511

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4874

9748

14622

19496

24370

<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:

0.126

AC:

19229

AN:

152168

Hom.:

1324

Cov.:

AF XY:

0.128

AC XY:

9496

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0769

AC:

3193

AN:

41540

American (AMR)

AF:

0.145

AC:

2220

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.149

AC:

518

AN:

3470

East Asian (EAS)

AF:

0.191

AC:

990

AN:

5178

South Asian (SAS)

AF:

0.202

AC:

974

AN:

4812

European-Finnish (FIN)

AF:

0.114

AC:

1204

AN:

10582

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.141

AC:

9615

AN:

67986

Other (OTH)

AF:

0.151

AC:

319

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

881

1762

2643

3524

4405

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

220

440

660

880

1100

<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:

0.130

Hom.:

612

Bravo

AF:

0.128

Asia WGS

AF:

0.203

AC:

705

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.6

(source)

DANN

Benign

0.41

PhyloP100

-1.5

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