17-11640293-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001372.4(DNAH9):c.1810A>G(p.Met604Val) variant causes a missense change. The variant allele was found at a frequency of 0.0257 in 1,613,072 control chromosomes in the GnomAD database, including 689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 58 hom., cov: 32)

Exomes 𝑓: 0.026 ( 631 hom. )

Consequence

DNAH9
NM_001372.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.88

Publications

9 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=0.011774987).

BP6

Variant 17-11640293-A-G is Benign according to our data. Variant chr17-11640293-A-G is described in ClinVar as Benign. ClinVar VariationId is 402775.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0203 (3098/152300) while in subpopulation SAS AF = 0.0304 (147/4828). AF 95% confidence interval is 0.0278. There are 58 homozygotes in GnomAd4. There are 1426 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 58 AR,AD gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH9	NM_001372.4	MANE Select	c.1810A>G	p.Met604Val	missense	Exon 10 of 69	NP_001363.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH9	ENST00000262442.9	TSL:1 MANE Select	c.1810A>G	p.Met604Val	missense	Exon 10 of 69	ENSP00000262442.3
	DNAH9	ENST00000454412.6	TSL:5	c.1810A>G	p.Met604Val	missense	Exon 10 of 68	ENSP00000414874.2

Frequencies

GnomAD3 genomes

AF:

0.0204

AC:

3099

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00507

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0184

Gnomad ASJ

AF:

0.0467

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0302

Gnomad FIN

AF:

0.0219

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0289

Gnomad OTH

AF:

0.0302

GnomAD2 exomes

AF:

0.0232

AC:

5834

AN:

251188

AF XY:

0.0251

show subpopulations

Gnomad AFR exome

AF:

0.00437

Gnomad AMR exome

AF:

0.0108

Gnomad ASJ exome

AF:

0.0440

Gnomad EAS exome

AF:

0.000381

Gnomad FIN exome

AF:

0.0226

Gnomad NFE exome

AF:

0.0296

Gnomad OTH exome

AF:

0.0258

GnomAD4 exome

AF:

0.0263

AC:

38398

AN:

1460772

Hom.:

631

Cov.:

AF XY:

0.0269

AC XY:

19568

AN XY:

726748

show subpopulations

African (AFR)

AF:

0.00404

AC:

135

AN:

33450

American (AMR)

AF:

0.0117

AC:

521

AN:

44658

Ashkenazi Jewish (ASJ)

AF:

0.0440

AC:

1148

AN:

26108

East Asian (EAS)

AF:

0.000126

AC:

AN:

39698

South Asian (SAS)

AF:

0.0322

AC:

2775

AN:

86212

European-Finnish (FIN)

AF:

0.0222

AC:

1188

AN:

53414

Middle Eastern (MID)

AF:

0.0535

AC:

308

AN:

5762

European-Non Finnish (NFE)

AF:

0.0278

AC:

30862

AN:

1111132

Other (OTH)

AF:

0.0241

AC:

1456

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

1663

3326

4990

6653

8316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1122

2244

3366

4488

5610

<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:

0.0203

AC:

3098

AN:

152300

Hom.:

Cov.:

AF XY:

0.0192

AC XY:

1426

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00505

AC:

210

AN:

41572

American (AMR)

AF:

0.0184

AC:

281

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0467

AC:

162

AN:

3468

East Asian (EAS)

AF:

0.000194

AC:

AN:

5166

South Asian (SAS)

AF:

0.0304

AC:

147

AN:

4828

European-Finnish (FIN)

AF:

0.0219

AC:

232

AN:

10616

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0289

AC:

1966

AN:

68026

Other (OTH)

AF:

0.0294

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

154

309

463

618

772

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.0280

Hom.:

218

Bravo

AF:

0.0196

TwinsUK

AF:

0.0286

AC:

106

ALSPAC

AF:

0.0278

AC:

107

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.0322

AC:

277

ExAC

AF:

0.0236

AC:

2863

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0300

EpiControl

AF:

0.0290

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.096

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.59

MutationAssessor

Uncertain

2.8

PhyloP100

4.9

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.3

REVEL

Uncertain

0.38

Sift

Benign

0.033

Polyphen

0.95

Vest4

0.13

MPC

0.14

ClinPred

0.026

GERP RS

5.4

Varity_R

0.45

gMVP

0.38

Mutation Taster

=94/6

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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