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. Variant has been reported in ClinVar as (no stars).

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366683.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DOCK9	NM_001366683.2	MANE Select	c.2043+18A>G	intron	N/A	NP_001353612.1	A0A804HIE8
DOCK9	NM_001366681.2		c.2043+18A>G	intron	N/A	NP_001353610.1
DOCK9	NM_001366684.2		c.2043+18A>G	intron	N/A	NP_001353613.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DOCK9	ENST00000682017.1	MANE Select	c.2043+18A>G	intron	N/A	ENSP00000507034.1	A0A804HIE8
DOCK9	ENST00000427887.2	TSL:1	c.2046+18A>G	intron	N/A	ENSP00000413781.2	A0A0A0MT38
DOCK9	ENST00000903387.1		c.2043+18A>G	intron	N/A	ENSP00000573446.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over