NM_001277115.2:c.11325G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001277115.2(DNAH11):c.11325G>A(p.Ala3775Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.054 in 1,613,346 control chromosomes in the GnomAD database, including 4,633 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 525 hom., cov: 32)

Exomes 𝑓: 0.054 ( 4108 hom. )

Consequence

DNAH11
NM_001277115.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.30

Publications

11 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.13).

BP6

Variant 7-21861975-G-A is Benign according to our data. Variant chr7-21861975-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 163127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.3 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.11325G>A	p.Ala3775Ala	synonymous_variant	Exon 69 of 82	ENST00000409508.8	NP_001264044.1	Q96DT5Q96NT7H9NAJ8H9NAJ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH11	ENST00000409508.8 link	c.11325G>A	p.Ala3775Ala	synonymous_variant	Exon 69 of 82	5	NM_001277115.2	ENSP00000475939.1	Q96DT5
DNAH11	ENST00000421290.1 link	n.508G>A		non_coding_transcript_exon_variant	Exon 4 of 4	4
DNAH11	ENST00000607413.5 link	n.*5G>A		downstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0559

AC:

8506

AN:

152120

Hom.:

515

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0120

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.0450

Gnomad EAS

AF:

0.203

Gnomad SAS

AF:

0.0706

Gnomad FIN

AF:

0.0706

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0458

Gnomad OTH

AF:

0.0545

GnomAD2 exomes

AF:

0.0915

AC:

22686

AN:

248056

AF XY:

0.0828

show subpopulations

Gnomad AFR exome

AF:

0.0108

Gnomad AMR exome

AF:

0.272

Gnomad ASJ exome

AF:

0.0431

Gnomad EAS exome

AF:

0.210

Gnomad FIN exome

AF:

0.0719

Gnomad NFE exome

AF:

0.0449

Gnomad OTH exome

AF:

0.0753

GnomAD4 exome

AF:

0.0538

AC:

78670

AN:

1461108

Hom.:

4108

Cov.:

AF XY:

0.0535

AC XY:

38913

AN XY:

726802

show subpopulations

African (AFR)

AF:

0.00795

AC:

266

AN:

33468

American (AMR)

AF:

0.261

AC:

11630

AN:

44596

Ashkenazi Jewish (ASJ)

AF:

0.0437

AC:

1143

AN:

26126

East Asian (EAS)

AF:

0.207

AC:

8209

AN:

39652

South Asian (SAS)

AF:

0.0632

AC:

5448

AN:

86154

European-Finnish (FIN)

AF:

0.0720

AC:

3843

AN:

53360

Middle Eastern (MID)

AF:

0.0322

AC:

185

AN:

5746

European-Non Finnish (NFE)

AF:

0.0401

AC:

44614

AN:

1111656

Other (OTH)

AF:

0.0552

AC:

3332

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

3667

7335

11002

14670

18337

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1768

3536

5304

7072

8840

<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:

0.0560

AC:

8524

AN:

152238

Hom.:

525

Cov.:

AF XY:

0.0605

AC XY:

4501

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0120

AC:

497

AN:

41552

American (AMR)

AF:

0.162

AC:

2473

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0450

AC:

156

AN:

3470

East Asian (EAS)

AF:

0.203

AC:

1053

AN:

5186

South Asian (SAS)

AF:

0.0710

AC:

343

AN:

4828

European-Finnish (FIN)

AF:

0.0706

AC:

748

AN:

10590

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0459

AC:

3118

AN:

67998

Other (OTH)

AF:

0.0530

AC:

112

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

387

775

1162

1550

1937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

294

392

490

<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:

0.0519

Hom.:

1534

Bravo

AF:

0.0644

Asia WGS

AF:

0.144

AC:

501

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

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Ala3775Ala in exon 69 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 4.3% (363/8394) o f European American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs12666072). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Nov 12, 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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.056

(source)

DANN

Benign

0.63

PhyloP100

-3.3

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