NM_001277115.2:c.2454A>G

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.2454A>G(p.Ala818Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 1,613,416 control chromosomes in the GnomAD database, including 148,040 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A818A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.45 ( 16236 hom., cov: 31)

Exomes 𝑓: 0.42 ( 131804 hom. )

Consequence

DNAH11
NM_001277115.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.914

Publications

16 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=-0.89).

BP6

Variant 7-21591364-A-G is Benign according to our data. Variant chr7-21591364-A-G is described in ClinVar as Benign. ClinVar VariationId is 93684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.914 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.2454A>G	p.Ala818Ala	synonymous_variant	Exon 14 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.2454A>G	p.Ala818Ala	synonymous_variant	Exon 14 of 82	5	NM_001277115.2	ENSP00000475939.1		Q96DT5

Frequencies

GnomAD3 genomes

AF:

0.451

AC:

68478

AN:

151740

Hom.:

16205

Cov.:

show subpopulations

Gnomad AFR

AF:

0.552

Gnomad AMI

AF:

0.160

Gnomad AMR

AF:

0.386

Gnomad ASJ

AF:

0.342

Gnomad EAS

AF:

0.781

Gnomad SAS

AF:

0.442

Gnomad FIN

AF:

0.392

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.400

Gnomad OTH

AF:

0.439

GnomAD2 exomes

AF:

0.428

AC:

106424

AN:

248642

AF XY:

0.428

show subpopulations

Gnomad AFR exome

AF:

0.548

Gnomad AMR exome

AF:

0.326

Gnomad ASJ exome

AF:

0.354

Gnomad EAS exome

AF:

0.782

Gnomad FIN exome

AF:

0.395

Gnomad NFE exome

AF:

0.402

Gnomad OTH exome

AF:

0.395

GnomAD4 exome

AF:

0.419

AC:

611928

AN:

1461558

Hom.:

131804

Cov.:

AF XY:

0.417

AC XY:

303393

AN XY:

727058

show subpopulations

African (AFR)

AF:

0.547

AC:

18303

AN:

33470

American (AMR)

AF:

0.336

AC:

15024

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.353

AC:

9228

AN:

26128

East Asian (EAS)

AF:

0.753

AC:

29900

AN:

39700

South Asian (SAS)

AF:

0.424

AC:

36545

AN:

86240

European-Finnish (FIN)

AF:

0.396

AC:

21142

AN:

53386

Middle Eastern (MID)

AF:

0.394

AC:

2270

AN:

5766

European-Non Finnish (NFE)

AF:

0.408

AC:

453284

AN:

1111774

Other (OTH)

AF:

0.434

AC:

26232

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

21332

42663

63995

85326

106658

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14246

28492

42738

56984

71230

<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:

0.451

AC:

68551

AN:

151858

Hom.:

16236

Cov.:

AF XY:

0.451

AC XY:

33499

AN XY:

74226

show subpopulations

African (AFR)

AF:

0.552

AC:

22854

AN:

41392

American (AMR)

AF:

0.385

AC:

5882

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.342

AC:

1189

AN:

3472

East Asian (EAS)

AF:

0.780

AC:

3993

AN:

5118

South Asian (SAS)

AF:

0.442

AC:

2113

AN:

4778

European-Finnish (FIN)

AF:

0.392

AC:

4149

AN:

10576

Middle Eastern (MID)

AF:

0.371

AC:

109

AN:

294

European-Non Finnish (NFE)

AF:

0.400

AC:

27192

AN:

67942

Other (OTH)

AF:

0.440

AC:

924

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1854

3708

5561

7415

9269

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

632

1264

1896

2528

3160

<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:

0.422

Hom.:

7696

Bravo

AF:

0.456

Asia WGS

AF:

0.605

AC:

2104

AN:

3478

EpiCase

AF:

0.396

EpiControl

AF:

0.398

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

Ala818Ala in exon 14 of DNAH11: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 48.2% (2040/4230) of African American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs4615458). -

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:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia 7

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

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

-0.89

CADD

Benign

0.53

(source)

DANN

Benign

0.40

PhyloP100

-0.91

Mutation Taster

=100/0

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