rs8071438

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is The variant received -17 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_StrongBP6_StrongBP7

The NM_001372.4(DNAH9):c.3369T>C (p.Asp1123Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.98 (AC=1,582,196) in the gnomAD database across 1,613,704 control chromosomes, including 776,019 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.986. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely Benign (★★).

Frequency

Genomes: 𝑓 0.97 ( 71261 hom., cov: 32)

Exomes 𝑓: 0.98 ( 704758 hom. )

Consequence

DNAH9
NM_001372.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.277

Publications

16 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: ClinGen, G2P, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
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

new If you want to explore the variant's impact on the transcript NM_001372.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -17 points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BP6

ClinVar 2-star benign — strong (BP6); ClinVar germline classification: Benign/Likely Benign, 2 star(s).

BP7

Synonymous variant at non-conserved position with no predicted splicing impact (BP7); Synonymous at non-conserved position, no splicing concern — benign (BP7).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.9864 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH9	NM_001372.4	MANE Select	c.3369T>C	p.Asp1123Asp	synonymous	Exon 18 of 69	NP_001363.2	Q9NYC9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH9	ENST00000262442.9	TSL:1 MANE Select	c.3369T>C	p.Asp1123Asp	synonymous	Exon 18 of 69	ENSP00000262442.3	Q9NYC9-1
	DNAH9	ENST00000454412.6	TSL:5	c.3369T>C	p.Asp1123Asp	synonymous	Exon 18 of 68	ENSP00000414874.2	E7EP17

Frequencies

GnomAD3 genomes

AF:

0.967

AC:

147142

AN:

152156

Hom.:

71210

Cov.:

show subpopulations

Gnomad AFR

AF:

0.929

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.971

Gnomad ASJ

AF:

0.969

Gnomad EAS

AF:

0.910

Gnomad SAS

AF:

0.963

Gnomad FIN

AF:

0.999

Gnomad MID

AF:

0.991

Gnomad NFE

AF:

0.988

Gnomad OTH

AF:

0.968

GnomAD2 exomes

AF:

0.972

AC:

244454

AN:

251422

AF XY:

0.974

show subpopulations

Gnomad AFR exome

AF:

0.928

Gnomad AMR exome

AF:

0.961

Gnomad ASJ exome

AF:

0.968

Gnomad EAS exome

AF:

0.912

Gnomad FIN exome

AF:

0.999

Gnomad NFE exome

AF:

0.989

Gnomad OTH exome

AF:

0.979

GnomAD4 exome

AF:

0.982

AC:

1434943

AN:

1461430

Hom.:

704758

Cov.:

AF XY:

0.982

AC XY:

713698

AN XY:

727070

show subpopulations

African (AFR)

AF:

0.929

AC:

31098

AN:

33468

American (AMR)

AF:

0.963

AC:

43047

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.968

AC:

25292

AN:

26130

East Asian (EAS)

AF:

0.906

AC:

35969

AN:

39692

South Asian (SAS)

AF:

0.966

AC:

83349

AN:

86242

European-Finnish (FIN)

AF:

0.999

AC:

53355

AN:

53414

Middle Eastern (MID)

AF:

0.979

AC:

5646

AN:

5768

European-Non Finnish (NFE)

AF:

0.988

AC:

1098277

AN:

1111618

Other (OTH)

AF:

0.976

AC:

58910

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

1262

2525

3787

5050

6312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21656

43312

64968

86624

108280

<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:

0.967

AC:

147253

AN:

152274

Hom.:

71261

Cov.:

AF XY:

0.968

AC XY:

72015

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.929

AC:

38586

AN:

41536

American (AMR)

AF:

0.971

AC:

14844

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.969

AC:

3366

AN:

3472

East Asian (EAS)

AF:

0.910

AC:

4708

AN:

5174

South Asian (SAS)

AF:

0.964

AC:

4645

AN:

4820

European-Finnish (FIN)

AF:

0.999

AC:

10607

AN:

10618

Middle Eastern (MID)

AF:

0.990

AC:

291

AN:

294

European-Non Finnish (NFE)

AF:

0.988

AC:

67252

AN:

68042

Other (OTH)

AF:

0.967

AC:

2042

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

241

483

724

966

1207

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

912

1824

2736

3648

4560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

TOPMed (Bravo)

AF:

0.962

ALFA (dbGaP/dbSNP Allele Frequency Aggregator)

AF:

0.978

AC:

221908

AN:

226866

Hom.:

108567

Local populations

ABraOM SABE-WGS-1171

AF:

0.962

AC:

2253

AN:

2342

Hom.:

1090

ChinaMAP Phase 1

AF:

0.910

Denmark Genome

AF:

1.00

AC:

300

AN:

300

ESP6500 (Exome Variant Server)

AF:

0.968

AC:

12594

AN:

13006

show subpopulations

European American

AF:

0.988

AC:

8497

AN:

8600

African American

AF:

0.930

AC:

4097

AN:

4406

GenomeAsia100K

AF:

0.923

AC:

3211

AN:

3478

show subpopulations

Oceania

AF:

0.696

AC:

103

AN:

148

Hom.:

North-East Asia

AF:

0.926

AC:

650

AN:

702

Hom.:

300

South-East Asia

AF:

0.905

AC:

626

AN:

692

Hom.:

282

South Asia

AF:

0.943

AC:

1366

AN:

1448

Hom.:

644

Africa

AF:

0.918

AC:

191

AN:

208

Hom.:

America

AF:

0.942

AC:

AN:

Hom.:

West Eurasia

AF:

0.991

AC:

226

AN:

228

Hom.:

112

Korea4K (4,157 Koreans)

AF:

0.924

AC:

6683

AN:

7232

Qatari Genome

AF:

0.984

AC:

1978

AN:

2010

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.899

AC:

110431

AN:

122806

Hom.:

49683

Turkish Variome

AF:

0.972

AC:

6538

AN:

6724

Hom.:

3183

UK10K

AF:

0.990

AC:

7485

AN:

7562

show subpopulations

TwinsUK

AF:

0.993

AC:

3548

AN:

3574

ALSPAC

AF:

0.988

AC:

3806

AN:

3854

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.910

AC:

8156

AN:

8960

Hom.:

3719

Case/control cohorts

Cohort

Cases

Controls

ASC

(Autism)

11043 / 11112AF: 0.993790

17503 / 17616AF: 0.993585

BipEx

(Bipolar disorder (including schizoaffective))

28159 / 28420AF: 0.990816

28549 / 28844AF: 0.989773

Epi25

(Epilepsy)

40946 / 41958AF: 0.975881

65439 / 66888AF: 0.978337

SCHEMA

(Schizophrenia)

158070 / 177146AF: 0.892315

268008 / 300016AF: 0.893312

Allele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Ciliary dyskinesia, primary, 40 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.32

(source)

DANN

Benign

0.25

PhyloP100

0.28

AlphaGenome AVI

Benign

0.84

(source)

GPN-Star LLR

2.2

(source)

GPN-Star score

-2.0

(source)

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

Pangolin (max)

Benign

0.0

(source)

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

Local populations

Case/control cohorts

ClinVar

Computational scores

Splicing

Publications

Other links and lift over