rs55666134

Variant names:

Variant summary

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

The NM_001277115.2(DNAH11):c.5490G>A(p.Leu1830Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,610,424 control chromosomes in the GnomAD database, including 17,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1229 hom., cov: 32)

Exomes 𝑓: 0.14 ( 16065 hom. )

Consequence

DNAH11
NM_001277115.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.377

Publications

15 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 7-21683813-G-A is Benign according to our data. Variant chr7-21683813-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 93691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.377 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.5490G>A	p.Leu1830Leu	synonymous_variant	Exon 32 of 82	ENST00000409508.8	NP_001264044.1	Q96DT5Q96NT7H9NAJ8H9NAJ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8 link	c.5490G>A	p.Leu1830Leu	synonymous_variant	Exon 32 of 82	5	NM_001277115.2	ENSP00000475939.1		Q96DT5

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17819

AN:

152060

Hom.:

1230

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0420

Gnomad AMI

AF:

0.139

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.159

Gnomad EAS

AF:

0.141

Gnomad SAS

AF:

0.111

Gnomad FIN

AF:

0.155

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.157

Gnomad OTH

AF:

0.119

GnomAD2 exomes

AF:

0.129

AC:

31967

AN:

247102

AF XY:

0.132

show subpopulations

Gnomad AFR exome

AF:

0.0372

Gnomad AMR exome

AF:

0.0725

Gnomad ASJ exome

AF:

0.153

Gnomad EAS exome

AF:

0.141

Gnomad FIN exome

AF:

0.157

Gnomad NFE exome

AF:

0.156

Gnomad OTH exome

AF:

0.132

GnomAD4 exome

AF:

0.145

AC:

211014

AN:

1458246

Hom.:

16065

Cov.:

AF XY:

0.144

AC XY:

104462

AN XY:

725222

show subpopulations

African (AFR)

AF:

0.0350

AC:

1170

AN:

33418

American (AMR)

AF:

0.0764

AC:

3396

AN:

44464

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

4075

AN:

25968

East Asian (EAS)

AF:

0.140

AC:

5549

AN:

39646

South Asian (SAS)

AF:

0.109

AC:

9349

AN:

85498

European-Finnish (FIN)

AF:

0.157

AC:

8344

AN:

53246

Middle Eastern (MID)

AF:

0.115

AC:

662

AN:

5748

European-Non Finnish (NFE)

AF:

0.153

AC:

170290

AN:

1110014

Other (OTH)

AF:

0.136

AC:

8179

AN:

60244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

9477

18955

28432

37910

47387

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6002

12004

18006

24008

30010

<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:

0.117

AC:

17820

AN:

152178

Hom.:

1229

Cov.:

AF XY:

0.117

AC XY:

8688

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0420

AC:

1747

AN:

41552

American (AMR)

AF:

0.101

AC:

1539

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.159

AC:

553

AN:

3468

East Asian (EAS)

AF:

0.141

AC:

732

AN:

5182

South Asian (SAS)

AF:

0.111

AC:

535

AN:

4818

European-Finnish (FIN)

AF:

0.155

AC:

1642

AN:

10568

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.157

AC:

10662

AN:

67978

Other (OTH)

AF:

0.118

AC:

250

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

779

1558

2338

3117

3896

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

200

400

600

800

1000

<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:

0.142

Hom.:

5828

Bravo

AF:

0.109

Asia WGS

AF:

0.123

AC:

427

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Apr 05, 2013

Eurofins Ntd Llc (ga)

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

Leu1830Leu in exon 32 of DNAH11: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 15.0% (1240/8258) of European American chromosomes from a broad population by the NHLBI Exome Seq uencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs55666134). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Primary ciliary dyskinesia 7

Benign:1

Oct 29, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely 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

-0.56

CADD

Benign

2.0

(source)

DANN

Benign

0.64

PhyloP100

0.38

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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