Genetic Variant DOCK9-DT:n.581T>A (chr13-99088399-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000562781.1(DOCK9-DT):n.581T>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 151,918 control chromosomes in the GnomAD database, including 7,493 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 0.31 ( 7491 hom., cov: 31)

Exomes 𝑓: 0.30 ( 2 hom. )

Consequence

DOCK9-DT
ENST00000562781.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.96

Publications

8 publications found

Variant links:

Genes affected

DOCK9-DT (HGNC:43696): (DOCK9 divergent transcript)

DOCK9-DT links:

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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK9-DT	NR_047482.1 link	n.1677T>A		non_coding_transcript_exon_variant	Exon 1 of 1
DOCK9	XM_047430231.1 link	c.-457A>T		5_prime_UTR_variant	Exon 1 of 56		XP_047286187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK9-DT	ENST00000562781.1 link	n.581T>A		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

AF:

0.307

AC:

46565

AN:

151768

Hom.:

7469

Cov.:

show subpopulations

Gnomad AFR

AF:

0.295

Gnomad AMI

AF:

0.293

Gnomad AMR

AF:

0.212

Gnomad ASJ

AF:

0.314

Gnomad EAS

AF:

0.428

Gnomad SAS

AF:

0.426

Gnomad FIN

AF:

0.314

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.316

Gnomad OTH

AF:

0.307

GnomAD4 exome

AF:

0.300

AC:

AN:

Hom.:

Cov.:

AF XY:

0.292

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.350

AC:

AN:

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.307

AC:

46621

AN:

151888

Hom.:

7491

Cov.:

AF XY:

0.309

AC XY:

22917

AN XY:

74208

show subpopulations

African (AFR)

AF:

0.296

AC:

12250

AN:

41400

American (AMR)

AF:

0.211

AC:

3232

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.314

AC:

1089

AN:

3470

East Asian (EAS)

AF:

0.428

AC:

2207

AN:

5154

South Asian (SAS)

AF:

0.426

AC:

2045

AN:

4802

European-Finnish (FIN)

AF:

0.314

AC:

3300

AN:

10520

Middle Eastern (MID)

AF:

0.286

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.316

AC:

21501

AN:

67952

Other (OTH)

AF:

0.307

AC:

646

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1593

3186

4780

6373

7966

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

494

988

1482

1976

2470

<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:

0.178

Hom.:

360

Bravo

AF:

0.294

Asia WGS

AF:

0.380

AC:

1320

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.12

(source)

DANN

Benign

0.51

PhyloP100

-2.0

Splicing

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