chr17-11598540-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_001372.4(DNAH9):c.42C>G(p.Asn14Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000327 in 1,402,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

DNAH9
NM_001372.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:2

Conservation

PhyloP100: -0.735

Publications

0 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P
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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0050899684).

BP6

Variant 17-11598540-C-G is Benign according to our data. Variant chr17-11598540-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 1570552.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00177 (260/146746) while in subpopulation AFR AF = 0.0059 (243/41204). AF 95% confidence interval is 0.00529. There are 0 homozygotes in GnomAd4. There are 116 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

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.42C>G	p.Asn14Lys	missense	Exon 1 of 69	NP_001363.2	Q9NYC9-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAH9	ENST00000262442.9	TSL:1 MANE Select	c.42C>G	p.Asn14Lys	missense	Exon 1 of 69	ENSP00000262442.3	Q9NYC9-1
DNAH9	ENST00000579406.1	TSL:1	n.69C>G		non_coding_transcript_exon	Exon 1 of 8
DNAH9	ENST00000454412.6	TSL:5	c.42C>G	p.Asn14Lys	missense	Exon 1 of 68	ENSP00000414874.2	E7EP17

Frequencies

GnomAD3 genomes

AF:

0.00177

AC:

259

AN:

146632

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00589

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000887

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00325

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00149

GnomAD2 exomes

AF:

0.000292

AC:

AN:

30774

AF XY:

0.000279

show subpopulations

Gnomad AFR exome

AF:

0.00884

Gnomad AMR exome

AF:

0.000331

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000159

AC:

199

AN:

1255522

Hom.:

Cov.:

AF XY:

0.000155

AC XY:

AN XY:

613442

show subpopulations

African (AFR)

AF:

0.00663

AC:

166

AN:

25026

American (AMR)

AF:

0.000436

AC:

AN:

16040

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19250

East Asian (EAS)

AF:

0.00

AC:

AN:

28050

South Asian (SAS)

AF:

0.00

AC:

AN:

60558

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30468

Middle Eastern (MID)

AF:

0.000533

AC:

AN:

3750

European-Non Finnish (NFE)

AF:

0.00000392

AC:

AN:

1020620

Other (OTH)

AF:

0.000386

AC:

AN:

51760

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00177

AC:

260

AN:

146746

Hom.:

Cov.:

AF XY:

0.00162

AC XY:

116

AN XY:

71574

show subpopulations

African (AFR)

AF:

0.00590

AC:

243

AN:

41204

American (AMR)

AF:

0.000886

AC:

AN:

14680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3422

East Asian (EAS)

AF:

0.00

AC:

AN:

5142

South Asian (SAS)

AF:

0.00

AC:

AN:

4700

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9662

Middle Eastern (MID)

AF:

0.00350

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

64882

Other (OTH)

AF:

0.00147

AC:

AN:

2036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00153

Hom.:

Bravo

AF:

0.00213

ExAC

AF:

0.000311

AC:

Asia WGS

AF:

0.000578

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

DNAH9-related disorder (1)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.55

(source)

DANN

Benign

0.45

DEOGEN2

Benign

0.0037

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.52

MetaRNN

Benign

0.0051

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.40

PhyloP100

-0.73

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.48

REVEL

Benign

0.015

Sift

Benign

0.79

Sift4G

Uncertain

0.036

Polyphen

0.0

Vest4

0.10

MutPred

0.28

Gain of ubiquitination at N14 (P = 0.0029)

MVP

0.13

MPC

0.11

ClinPred

0.0037

GERP RS

-0.63

PromoterAI

0.11

Neutral

(source)

Varity_R

0.032

gMVP

0.27

Mutation Taster

=97/3

polymorphism

(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