Genetic Variant DNAH9:c.12106-10C>T (chr17-11932004-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001372.4(DNAH9):c.12106-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,612,952 control chromosomes in the GnomAD database, including 25,633 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2354 hom., cov: 32)

Exomes 𝑓: 0.18 ( 23279 hom. )

Consequence

DNAH9
NM_001372.4 intron

Scores

Splicing: ADA: 0.00002495

Clinical Significance

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

Conservation

PhyloP100: -0.130

Publications

14 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 17-11932004-C-T is Benign according to our data. Variant chr17-11932004-C-T is described in ClinVar as Benign. ClinVar VariationId is 402786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

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.12106-10C>T		intron	N/A	NP_001363.2	Q9NYC9-1
	DNAH9	NM_004662.2		c.1042-10C>T		intron	N/A	NP_004653.2	Q99499

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DNAH9	ENST00000262442.9	TSL:1 MANE Select	c.12106-10C>T	intron	N/A	ENSP00000262442.3	Q9NYC9-1
DNAH9	ENST00000608377.5	TSL:1	c.1042-10C>T	intron	N/A	ENSP00000476951.1	Q9NYC9-3
DNAH9	ENST00000396001.6	TSL:1	n.1569-10C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.173

AC:

26312

AN:

151956

Hom.:

2347

Cov.:

show subpopulations

Gnomad AFR

AF:

0.143

Gnomad AMI

AF:

0.309

Gnomad AMR

AF:

0.207

Gnomad ASJ

AF:

0.155

Gnomad EAS

AF:

0.196

Gnomad SAS

AF:

0.141

Gnomad FIN

AF:

0.197

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.180

Gnomad OTH

AF:

0.175

GnomAD2 exomes

AF:

0.185

AC:

46446

AN:

250842

AF XY:

0.180

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.276

Gnomad ASJ exome

AF:

0.150

Gnomad EAS exome

AF:

0.194

Gnomad FIN exome

AF:

0.193

Gnomad NFE exome

AF:

0.177

Gnomad OTH exome

AF:

0.184

GnomAD4 exome

AF:

0.176

AC:

257467

AN:

1460876

Hom.:

23279

Cov.:

AF XY:

0.174

AC XY:

126648

AN XY:

726644

show subpopulations

African (AFR)

AF:

0.142

AC:

4736

AN:

33452

American (AMR)

AF:

0.265

AC:

11842

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.153

AC:

3985

AN:

26102

East Asian (EAS)

AF:

0.181

AC:

7179

AN:

39680

South Asian (SAS)

AF:

0.140

AC:

12072

AN:

86218

European-Finnish (FIN)

AF:

0.193

AC:

10333

AN:

53414

Middle Eastern (MID)

AF:

0.169

AC:

973

AN:

5744

European-Non Finnish (NFE)

AF:

0.176

AC:

195811

AN:

1111240

Other (OTH)

AF:

0.175

AC:

10536

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

10838

21677

32515

43354

54192

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6970

13940

20910

27880

34850

<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:

26330

AN:

152076

Hom.:

2354

Cov.:

AF XY:

0.173

AC XY:

12838

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.143

AC:

5921

AN:

41484

American (AMR)

AF:

0.207

AC:

3166

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.155

AC:

539

AN:

3470

East Asian (EAS)

AF:

0.195

AC:

1009

AN:

5176

South Asian (SAS)

AF:

0.141

AC:

675

AN:

4790

European-Finnish (FIN)

AF:

0.197

AC:

2085

AN:

10586

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.180

AC:

12221

AN:

67988

Other (OTH)

AF:

0.176

AC:

371

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1110

2220

3329

4439

5549

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

286

572

858

1144

1430

<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:

0.180

Hom.:

4437

Bravo

AF:

0.177

Asia WGS

AF:

0.159

AC:

551

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.4

(source)

DANN

Benign

0.78

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000025

dbscSNV1_RF

Benign

0.048

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

Computational scores

Splicing

Publications

Other links and lift over