17-11745015-C-T

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.6330C>T(p.Asn2110Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 1,613,622 control chromosomes in the GnomAD database, including 502,233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 42796 hom., cov: 32)

Exomes 𝑓: 0.79 ( 459437 hom. )

Consequence

DNAH9
NM_001372.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.437

Publications

20 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=-0.5).

BP6

Variant 17-11745015-C-T is Benign according to our data. Variant chr17-11745015-C-T is described in ClinVar as Benign. ClinVar VariationId is 402777.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.437 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH9	NM_001372.4 link	c.6330C>T	p.Asn2110Asn	synonymous_variant	Exon 31 of 69	ENST00000262442.9	NP_001363.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH9	ENST00000262442.9 link	c.6330C>T	p.Asn2110Asn	synonymous_variant	Exon 31 of 69	1	NM_001372.4	ENSP00000262442.3
DNAH9	ENST00000454412.6 link	c.6330C>T	p.Asn2110Asn	synonymous_variant	Exon 31 of 68	5		ENSP00000414874.2

Frequencies

GnomAD3 genomes

AF:

0.745

AC:

113168

AN:

151924

Hom.:

42773

Cov.:

show subpopulations

Gnomad AFR

AF:

0.602

Gnomad AMI

AF:

0.768

Gnomad AMR

AF:

0.833

Gnomad ASJ

AF:

0.769

Gnomad EAS

AF:

0.916

Gnomad SAS

AF:

0.797

Gnomad FIN

AF:

0.723

Gnomad MID

AF:

0.763

Gnomad NFE

AF:

0.796

Gnomad OTH

AF:

0.778

GnomAD2 exomes

AF:

0.797

AC:

200377

AN:

251276

AF XY:

0.797

show subpopulations

Gnomad AFR exome

AF:

0.599

Gnomad AMR exome

AF:

0.879

Gnomad ASJ exome

AF:

0.771

Gnomad EAS exome

AF:

0.912

Gnomad FIN exome

AF:

0.728

Gnomad NFE exome

AF:

0.801

Gnomad OTH exome

AF:

0.801

GnomAD4 exome

AF:

0.791

AC:

1156618

AN:

1461580

Hom.:

459437

Cov.:

AF XY:

0.791

AC XY:

575471

AN XY:

727080

show subpopulations

African (AFR)

AF:

0.592

AC:

19819

AN:

33470

American (AMR)

AF:

0.873

AC:

39028

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.776

AC:

20270

AN:

26132

East Asian (EAS)

AF:

0.917

AC:

36391

AN:

39696

South Asian (SAS)

AF:

0.787

AC:

67838

AN:

86248

European-Finnish (FIN)

AF:

0.737

AC:

39381

AN:

53418

Middle Eastern (MID)

AF:

0.756

AC:

4363

AN:

5768

European-Non Finnish (NFE)

AF:

0.794

AC:

882523

AN:

1111748

Other (OTH)

AF:

0.778

AC:

47005

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

12271

24541

36812

49082

61353

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20702

41404

62106

82808

103510

<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:

0.745

AC:

113240

AN:

152042

Hom.:

42796

Cov.:

AF XY:

0.746

AC XY:

55426

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.602

AC:

24956

AN:

41446

American (AMR)

AF:

0.833

AC:

12738

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.769

AC:

2670

AN:

3470

East Asian (EAS)

AF:

0.916

AC:

4717

AN:

5148

South Asian (SAS)

AF:

0.797

AC:

3838

AN:

4818

European-Finnish (FIN)

AF:

0.723

AC:

7649

AN:

10580

Middle Eastern (MID)

AF:

0.762

AC:

224

AN:

294

European-Non Finnish (NFE)

AF:

0.796

AC:

54097

AN:

67976

Other (OTH)

AF:

0.781

AC:

1652

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1427

2854

4281

5708

7135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

852

1704

2556

3408

4260

<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:

0.785

Hom.:

193662

Bravo

AF:

0.747

Asia WGS

AF:

0.831

AC:

2890

AN:

3478

EpiCase

AF:

0.798

EpiControl

AF:

0.801

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 24, 2020

GeneDx

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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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 -

Ciliary dyskinesia, primary, 40

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

1.6

(source)

DANN

Benign

0.71

PhyloP100

0.44

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over