chr7-21739660-A-G

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.7901A>G(p.Asn2634Ser) variant causes a missense change. The variant allele was found at a frequency of 0.598 in 1,610,198 control chromosomes in the GnomAD database, including 300,973 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N2634I) has been classified as Benign.

Frequency

Genomes: 𝑓 0.50 ( 21691 hom., cov: 31)

Exomes 𝑓: 0.61 ( 279282 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 4.52

Publications

23 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 (MetaRNN=6.6290036E-6).

BP6

Variant 7-21739660-A-G is Benign according to our data. Variant chr7-21739660-A-G is described in ClinVar as Benign. ClinVar VariationId is 163113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.7901A>G	p.Asn2634Ser	missense_variant	Exon 48 of 82	ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8 link	c.7901A>G	p.Asn2634Ser	missense_variant	Exon 48 of 82	5	NM_001277115.2	ENSP00000475939.1
DNAH11	ENST00000605912.1 link	c.461A>G	p.Asn154Ser	missense_variant	Exon 3 of 4	3		ENSP00000476068.1

Frequencies

GnomAD3 genomes

AF:

0.503

AC:

76446

AN:

151882

Hom.:

21691

Cov.:

show subpopulations

Gnomad AFR

AF:

0.275

Gnomad AMI

AF:

0.708

Gnomad AMR

AF:

0.516

Gnomad ASJ

AF:

0.544

Gnomad EAS

AF:

0.0805

Gnomad SAS

AF:

0.523

Gnomad FIN

AF:

0.650

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.642

Gnomad OTH

AF:

0.523

GnomAD2 exomes

AF:

0.533

AC:

132060

AN:

247692

AF XY:

0.547

show subpopulations

Gnomad AFR exome

AF:

0.261

Gnomad AMR exome

AF:

0.465

Gnomad ASJ exome

AF:

0.531

Gnomad EAS exome

AF:

0.0627

Gnomad FIN exome

AF:

0.641

Gnomad NFE exome

AF:

0.639

Gnomad OTH exome

AF:

0.565

GnomAD4 exome

AF:

0.608

AC:

886408

AN:

1458198

Hom.:

279282

Cov.:

AF XY:

0.608

AC XY:

441264

AN XY:

725280

show subpopulations

African (AFR)

AF:

0.267

AC:

8893

AN:

33342

American (AMR)

AF:

0.472

AC:

21010

AN:

44528

Ashkenazi Jewish (ASJ)

AF:

0.528

AC:

13785

AN:

26100

East Asian (EAS)

AF:

0.111

AC:

4409

AN:

39664

South Asian (SAS)

AF:

0.558

AC:

47728

AN:

85458

European-Finnish (FIN)

AF:

0.641

AC:

34202

AN:

53368

Middle Eastern (MID)

AF:

0.527

AC:

3034

AN:

5758

European-Non Finnish (NFE)

AF:

0.648

AC:

719463

AN:

1109738

Other (OTH)

AF:

0.562

AC:

33884

AN:

60242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

15981

31962

47942

63923

79904

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18540

37080

55620

74160

92700

<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:

0.503

AC:

76463

AN:

152000

Hom.:

21691

Cov.:

AF XY:

0.501

AC XY:

37218

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.275

AC:

11377

AN:

41442

American (AMR)

AF:

0.515

AC:

7866

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.544

AC:

1887

AN:

3466

East Asian (EAS)

AF:

0.0803

AC:

414

AN:

5154

South Asian (SAS)

AF:

0.523

AC:

2518

AN:

4814

European-Finnish (FIN)

AF:

0.650

AC:

6882

AN:

10590

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.642

AC:

43641

AN:

67954

Other (OTH)

AF:

0.524

AC:

1105

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1689

3378

5068

6757

8446

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

662

1324

1986

2648

3310

<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:

0.581

Hom.:

81783

Bravo

AF:

0.477

TwinsUK

AF:

0.647

AC:

2398

ALSPAC

AF:

0.649

AC:

2503

ESP6500AA

AF:

0.310

AC:

1187

ESP6500EA

AF:

0.634

AC:

5231

ExAC

AF:

0.534

AC:

64469

Asia WGS

AF:

0.320

AC:

1112

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

- -

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Asn2634Ser in exon 48 of DNAH11: This variant is not expected to have clinical s ignificance because it has been identified in 36.6% (3021/8252) of European Amer ican chromosomes from a broad population by the NHLBI Exome Sequencing Project ( http://evs.gs.washington.edu/EVS; dbSNP rs9639393). -

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

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.27

.;.;T;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.34

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.68

T;T;T;T

MetaRNN

Benign

0.0000066

T;T;T;T

MetaSVM

Benign

-0.97

PhyloP100

4.5

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.5

.;D;.;.

REVEL

Benign

0.19

Sift

Benign

0.051

.;T;.;.

Sift4G

Benign

0.26

.;.;.;T

Vest4

0.080

ClinPred

0.029

GERP RS

3.3

Varity_R

0.075

gMVP

0.16

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