chr17-11769290-G-T

Variant names:

Variant summary

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

The NM_001372.4(DNAH9):c.7513G>T(p.Val2505Leu) variant causes a missense change. The variant allele was found at a frequency of 0.137 in 1,613,640 control chromosomes in the GnomAD database, including 16,839 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V2505M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.10 ( 1094 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15745 hom. )

Consequence

DNAH9
NM_001372.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 6.84

Publications

14 publications found

Variant links:

Genes affected

DNAH9 (HGNC:2953): (dynein axonemal heavy chain 9) This gene encodes the heavy chain subunit of axonemal dynein, a large multi-subunit molecular motor. Axonemal dynein attaches to microtubules and hydrolyzes ATP to mediate the movement of cilia and flagella. The gene expresses at least two transcript variants; additional variants have been described, but their full length nature has not been determined. [provided by RefSeq, Jul 2008]

DNAH9 Gene-Disease associations (from GenCC):

ciliary dyskinesia, primary, 40
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
situs inversus
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
schizophrenia
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

DNAH9 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=0.0022479594).

BP6

Variant 17-11769290-G-T is Benign according to our data. Variant chr17-11769290-G-T is described in ClinVar as Benign. ClinVar VariationId is 402779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH9	NM_001372.4	MANE Select	c.7513G>T	p.Val2505Leu	missense	Exon 38 of 69	NP_001363.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH9	ENST00000262442.9	TSL:1 MANE Select	c.7513G>T	p.Val2505Leu	missense	Exon 38 of 69	ENSP00000262442.3
	DNAH9	ENST00000454412.6	TSL:5	c.7513G>T	p.Val2505Leu	missense	Exon 38 of 68	ENSP00000414874.2

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15849

AN:

152044

Hom.:

1096

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0286

Gnomad AMI

AF:

0.0954

Gnomad AMR

AF:

0.0930

Gnomad ASJ

AF:

0.160

Gnomad EAS

AF:

0.0360

Gnomad SAS

AF:

0.0989

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.146

Gnomad OTH

AF:

0.119

GnomAD2 exomes

AF:

0.115

AC:

28800

AN:

250298

AF XY:

0.118

show subpopulations

Gnomad AFR exome

AF:

0.0239

Gnomad AMR exome

AF:

0.0732

Gnomad ASJ exome

AF:

0.152

Gnomad EAS exome

AF:

0.0459

Gnomad FIN exome

AF:

0.154

Gnomad NFE exome

AF:

0.146

Gnomad OTH exome

AF:

0.125

GnomAD4 exome

AF:

0.141

AC:

205677

AN:

1461478

Hom.:

15745

Cov.:

AF XY:

0.139

AC XY:

101183

AN XY:

727010

show subpopulations

African (AFR)

AF:

0.0221

AC:

740

AN:

33480

American (AMR)

AF:

0.0758

AC:

3386

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

3924

AN:

26124

East Asian (EAS)

AF:

0.0283

AC:

1123

AN:

39692

South Asian (SAS)

AF:

0.0929

AC:

8010

AN:

86218

European-Finnish (FIN)

AF:

0.153

AC:

8158

AN:

53362

Middle Eastern (MID)

AF:

0.0923

AC:

531

AN:

5752

European-Non Finnish (NFE)

AF:

0.155

AC:

172062

AN:

1111776

Other (OTH)

AF:

0.128

AC:

7743

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

10648

21296

31945

42593

53241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6072

12144

18216

24288

30360

<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:

0.104

AC:

15841

AN:

152162

Hom.:

1094

Cov.:

AF XY:

0.106

AC XY:

7864

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0285

AC:

1185

AN:

41558

American (AMR)

AF:

0.0928

AC:

1419

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.160

AC:

555

AN:

3468

East Asian (EAS)

AF:

0.0357

AC:

184

AN:

5158

South Asian (SAS)

AF:

0.0981

AC:

472

AN:

4810

European-Finnish (FIN)

AF:

0.161

AC:

1710

AN:

10600

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.146

AC:

9940

AN:

67966

Other (OTH)

AF:

0.119

AC:

251

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

715

1430

2146

2861

3576

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

376

564

752

940

<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:

0.128

Hom.:

4643

Bravo

AF:

0.0957

TwinsUK

AF:

0.165

AC:

613

ALSPAC

AF:

0.162

AC:

624

ESP6500AA

AF:

0.0293

AC:

129

ESP6500EA

AF:

0.147

AC:

1268

ExAC

AF:

0.114

AC:

13796

Asia WGS

AF:

0.0750

AC:

261

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.076

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.9

PhyloP100

6.8

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.24

Sift

Uncertain

0.0040

Polyphen

0.98

Vest4

0.32

MutPred

0.80

Loss of methylation at K2503 (P = 0.0697)

MPC

0.26

ClinPred

0.011

GERP RS

4.4

Varity_R

0.59

gMVP

0.31

Mutation Taster

=99/1

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