rs17745898

Variant names:

Variant summary

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

The NM_001277115.2(DNAH11):c.3256-10C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,610,006 control chromosomes in the GnomAD database, including 17,377 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1127 hom., cov: 32)

Exomes 𝑓: 0.14 ( 16250 hom. )

Consequence

DNAH11
NM_001277115.2 intron

Scores

Splicing: ADA: 0.0001173

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.160

Publications

12 publications found

Variant links:

Genes affected

DNAH11 (HGNC:2942): (dynein axonemal heavy chain 11) This gene encodes a ciliary outer dynein arm protein and is a member of the dynein heavy chain family. It is a microtubule-dependent motor ATPase and has been reported to be involved in the movement of respiratory cilia. Mutations in this gene have been implicated in causing Kartagener Syndrome (a combination of situs inversus totalis and Primary Ciliary Dyskinesia (PCD), also called Immotile Cilia Syndrome 1 (ICS1)) and male sterility. [provided by RefSeq, Mar 2013]

DNAH11 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 7
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAH11 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=-0.83).

BP6

Variant 7-21601000-C-G is Benign according to our data. Variant chr7-21601000-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 163101.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.3256-10C>G		intron_variant	Intron 16 of 81	ENST00000409508.8	NP_001264044.1	Q96DT5Q96NT7H9NAJ8H9NAJ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8 link	c.3256-10C>G		intron_variant	Intron 16 of 81	5	NM_001277115.2	ENSP00000475939.1		Q96DT5

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16121

AN:

152064

Hom.:

1127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0275

Gnomad AMI

AF:

0.0385

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.0358

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.0853

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.157

Gnomad OTH

AF:

0.131

GnomAD2 exomes

AF:

0.116

AC:

28516

AN:

244890

AF XY:

0.122

show subpopulations

Gnomad AFR exome

AF:

0.0234

Gnomad AMR exome

AF:

0.0737

Gnomad ASJ exome

AF:

0.155

Gnomad EAS exome

AF:

0.0324

Gnomad FIN exome

AF:

0.0832

Gnomad NFE exome

AF:

0.155

Gnomad OTH exome

AF:

0.132

GnomAD4 exome

AF:

0.144

AC:

210202

AN:

1457822

Hom.:

16250

Cov.:

AF XY:

0.144

AC XY:

104662

AN XY:

725008

show subpopulations

African (AFR)

AF:

0.0224

AC:

740

AN:

33096

American (AMR)

AF:

0.0790

AC:

3449

AN:

43648

Ashkenazi Jewish (ASJ)

AF:

0.158

AC:

4106

AN:

26064

East Asian (EAS)

AF:

0.0257

AC:

1019

AN:

39676

South Asian (SAS)

AF:

0.125

AC:

10641

AN:

85008

European-Finnish (FIN)

AF:

0.0874

AC:

4662

AN:

53362

Middle Eastern (MID)

AF:

0.167

AC:

957

AN:

5746

European-Non Finnish (NFE)

AF:

0.159

AC:

176387

AN:

1110994

Other (OTH)

AF:

0.137

AC:

8241

AN:

60228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

10154

20308

30462

40616

50770

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6162

12324

18486

24648

30810

<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:

0.106

AC:

16122

AN:

152184

Hom.:

1127

Cov.:

AF XY:

0.103

AC XY:

7656

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0275

AC:

1141

AN:

41514

American (AMR)

AF:

0.112

AC:

1710

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

574

AN:

3470

East Asian (EAS)

AF:

0.0359

AC:

186

AN:

5186

South Asian (SAS)

AF:

0.118

AC:

569

AN:

4820

European-Finnish (FIN)

AF:

0.0853

AC:

904

AN:

10594

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.157

AC:

10690

AN:

67996

Other (OTH)

AF:

0.129

AC:

272

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

713

1425

2138

2850

3563

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

376

564

752

940

<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:

0.129

Hom.:

277

Bravo

AF:

0.105

Asia WGS

AF:

0.0550

AC:

195

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

3256-10C>G in intron 16 of DNAH11: This variant is not expected to have clinical significance because it has been identified in 15.9% (1304/8180) of European Am erican chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs17745898). -

Primary ciliary dyskinesia

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 10, 2018

GeneDx

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

-0.83

CADD

Benign

8.6

(source)

DANN

Benign

0.33

PhyloP100

0.16

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00012

dbscSNV1_RF

Benign

0.042

SpliceAI score (max)

0.080

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