rs1990236

Variant names:

Variant summary

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

The ENST00000262442.9(DNAH9):c.13122G>A(p.Met4374Ile) variant causes a missense change. The variant allele was found at a frequency of 0.182 in 1,613,930 control chromosomes in the GnomAD database, including 27,520 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2395 hom., cov: 32)

Exomes 𝑓: 0.18 ( 25125 hom. )

Consequence

DNAH9
ENST00000262442.9 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.83

Publications

33 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:

ENSG00000266368 (HGNC:):

ENSG00000266368 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=0.001670748).

BP6

Variant 17-11962145-G-A is Benign according to our data. Variant chr17-11962145-G-A is described in ClinVar as Benign. ClinVar VariationId is 402788.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000262442.9. 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.13122G>A	p.Met4374Ile	missense	Exon 68 of 69	NP_001363.2
	DNAH9	NM_004662.2		c.2058G>A	p.Met686Ile	missense	Exon 14 of 15	NP_004653.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DNAH9	ENST00000262442.9	TSL:1 MANE Select	c.13122G>A	p.Met4374Ile	missense	Exon 68 of 69	ENSP00000262442.3
DNAH9	ENST00000608377.5	TSL:1	c.2058G>A	p.Met686Ile	missense	Exon 14 of 15	ENSP00000476951.1
DNAH9	ENST00000396001.6	TSL:1	n.2585G>A		non_coding_transcript_exon	Exon 14 of 15

Frequencies

GnomAD3 genomes

AF:

0.173

AC:

26329

AN:

151962

Hom.:

2390

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.310

Gnomad AMR

AF:

0.210

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.209

Gnomad MID

AF:

0.191

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.177

GnomAD2 exomes

AF:

0.190

AC:

47605

AN:

250890

AF XY:

0.185

show subpopulations

Gnomad AFR exome

AF:

0.124

Gnomad AMR exome

AF:

0.282

Gnomad ASJ exome

AF:

0.160

Gnomad EAS exome

AF:

0.192

Gnomad FIN exome

AF:

0.204

Gnomad NFE exome

AF:

0.183

Gnomad OTH exome

AF:

0.193

GnomAD4 exome

AF:

0.183

AC:

267642

AN:

1461850

Hom.:

25125

Cov.:

AF XY:

0.181

AC XY:

131611

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.123

AC:

4122

AN:

33478

American (AMR)

AF:

0.270

AC:

12090

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.162

AC:

4221

AN:

26136

East Asian (EAS)

AF:

0.181

AC:

7202

AN:

39698

South Asian (SAS)

AF:

0.144

AC:

12412

AN:

86258

European-Finnish (FIN)

AF:

0.205

AC:

10924

AN:

53388

Middle Eastern (MID)

AF:

0.168

AC:

968

AN:

5768

European-Non Finnish (NFE)

AF:

0.184

AC:

204774

AN:

1112006

Other (OTH)

AF:

0.181

AC:

10929

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

13879

27758

41637

55516

69395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7278

14556

21834

29112

36390

<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:

0.173

AC:

26356

AN:

152080

Hom.:

2395

Cov.:

AF XY:

0.173

AC XY:

12895

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.129

AC:

5356

AN:

41498

American (AMR)

AF:

0.210

AC:

3210

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

574

AN:

3470

East Asian (EAS)

AF:

0.191

AC:

985

AN:

5148

South Asian (SAS)

AF:

0.145

AC:

700

AN:

4820

European-Finnish (FIN)

AF:

0.209

AC:

2203

AN:

10558

Middle Eastern (MID)

AF:

0.202

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.185

AC:

12609

AN:

67988

Other (OTH)

AF:

0.178

AC:

377

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1112

2224

3335

4447

5559

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

284

568

852

1136

1420

<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:

0.182

Hom.:

12045

Bravo

AF:

0.176

TwinsUK

AF:

0.196

AC:

727

ALSPAC

AF:

0.187

AC:

719

ESP6500AA

AF:

0.126

AC:

555

ESP6500EA

AF:

0.179

AC:

1538

ExAC

AF:

0.184

AC:

22337

Asia WGS

AF:

0.156

AC:

542

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

0.61

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.064

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.75

MetaRNN

Benign

0.0017

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.5

PhyloP100

6.8

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.15

Sift

Uncertain

0.021

Sift4G

Uncertain

0.032

Polyphen

0.35

Vest4

0.21

MutPred

0.61

Loss of disorder (P = 0.0837)

MPC

0.15

ClinPred

0.018

GERP RS

4.0

Varity_R

0.62

gMVP

0.41

Mutation Taster

=83/17

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over