rs9895535

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001372.4(DNAH9):c.1452A>G(p.Glu484Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 1,613,356 control chromosomes in the GnomAD database, including 88,842 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 15692 hom., cov: 32)

Exomes 𝑓: 0.31 ( 73150 hom. )

Consequence

DNAH9
NM_001372.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.516

Publications

12 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 17-11629518-A-G is Benign according to our data. Variant chr17-11629518-A-G is described in ClinVar as Benign. ClinVar VariationId is 402774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.516 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH9	NM_001372.4 link	c.1452A>G	p.Glu484Glu	synonymous_variant	Exon 7 of 69	ENST00000262442.9	NP_001363.2	Q9NYC9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH9	ENST00000262442.9 link	c.1452A>G	p.Glu484Glu	synonymous_variant	Exon 7 of 69	1	NM_001372.4	ENSP00000262442.3	Q9NYC9-1
DNAH9	ENST00000579406.1 link	n.1479A>G		non_coding_transcript_exon_variant	Exon 7 of 8	1
DNAH9	ENST00000454412.6 link	c.1452A>G	p.Glu484Glu	synonymous_variant	Exon 7 of 68	5		ENSP00000414874.2	E7EP17

Frequencies

GnomAD3 genomes

AF:

0.412

AC:

62548

AN:

151896

Hom.:

15649

Cov.:

show subpopulations

Gnomad AFR

AF:

0.712

Gnomad AMI

AF:

0.285

Gnomad AMR

AF:

0.293

Gnomad ASJ

AF:

0.269

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.325

Gnomad FIN

AF:

0.375

Gnomad MID

AF:

0.337

Gnomad NFE

AF:

0.299

Gnomad OTH

AF:

0.364

GnomAD2 exomes

AF:

0.312

AC:

78383

AN:

251362

AF XY:

0.308

show subpopulations

Gnomad AFR exome

AF:

0.732

Gnomad AMR exome

AF:

0.220

Gnomad ASJ exome

AF:

0.255

Gnomad EAS exome

AF:

0.145

Gnomad FIN exome

AF:

0.367

Gnomad NFE exome

AF:

0.300

Gnomad OTH exome

AF:

0.309

GnomAD4 exome

AF:

0.305

AC:

446383

AN:

1461338

Hom.:

73150

Cov.:

AF XY:

0.304

AC XY:

220830

AN XY:

727014

show subpopulations

African (AFR)

AF:

0.741

AC:

24790

AN:

33462

American (AMR)

AF:

0.229

AC:

10248

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.255

AC:

6659

AN:

26130

East Asian (EAS)

AF:

0.138

AC:

5482

AN:

39696

South Asian (SAS)

AF:

0.312

AC:

26903

AN:

86220

European-Finnish (FIN)

AF:

0.357

AC:

19057

AN:

53390

Middle Eastern (MID)

AF:

0.291

AC:

1674

AN:

5758

European-Non Finnish (NFE)

AF:

0.299

AC:

332094

AN:

1111576

Other (OTH)

AF:

0.323

AC:

19476

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

14408

28816

43223

57631

72039

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11060

22120

33180

44240

55300

<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:

0.412

AC:

62645

AN:

152018

Hom.:

15692

Cov.:

AF XY:

0.411

AC XY:

30528

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.712

AC:

29514

AN:

41448

American (AMR)

AF:

0.292

AC:

4464

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.269

AC:

934

AN:

3470

East Asian (EAS)

AF:

0.147

AC:

756

AN:

5154

South Asian (SAS)

AF:

0.323

AC:

1557

AN:

4818

European-Finnish (FIN)

AF:

0.375

AC:

3962

AN:

10574

Middle Eastern (MID)

AF:

0.337

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.299

AC:

20328

AN:

67962

Other (OTH)

AF:

0.366

AC:

772

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1641

3282

4923

6564

8205

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

554

1108

1662

2216

2770

<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:

0.354

Hom.:

5686

Bravo

AF:

0.417

Asia WGS

AF:

0.310

AC:

1078

AN:

3478

EpiCase

AF:

0.302

EpiControl

AF:

0.305

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.2

(source)

DANN

Benign

0.45

PhyloP100

-0.52

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over