NM_001277115.2:c.1916A>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.1916A>G(p.Gln639Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,612,248 control chromosomes in the GnomAD database, including 21,350 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q639W) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.15 ( 1762 hom., cov: 33)

Exomes 𝑓: 0.16 ( 19588 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.88

Publications

20 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=0.0027352571).

BP6

Variant 7-21588579-A-G is Benign according to our data. Variant chr7-21588579-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 163096.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.1916A>G	p.Gln639Arg	missense_variant	Exon 11 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.1916A>G	p.Gln639Arg	missense_variant	Exon 11 of 82	5	NM_001277115.2	ENSP00000475939.1		Q96DT5

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

23006

AN:

152146

Hom.:

1762

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.194

Gnomad EAS

AF:

0.196

Gnomad SAS

AF:

0.122

Gnomad FIN

AF:

0.128

Gnomad MID

AF:

0.172

Gnomad NFE

AF:

0.168

Gnomad OTH

AF:

0.174

GnomAD2 exomes

AF:

0.146

AC:

36443

AN:

248812

AF XY:

0.149

show subpopulations

Gnomad AFR exome

AF:

0.131

Gnomad AMR exome

AF:

0.0817

Gnomad ASJ exome

AF:

0.188

Gnomad EAS exome

AF:

0.198

Gnomad FIN exome

AF:

0.123

Gnomad NFE exome

AF:

0.166

Gnomad OTH exome

AF:

0.151

GnomAD4 exome

AF:

0.161

AC:

235078

AN:

1459984

Hom.:

19588

Cov.:

AF XY:

0.160

AC XY:

116533

AN XY:

726350

show subpopulations

African (AFR)

AF:

0.126

AC:

4231

AN:

33464

American (AMR)

AF:

0.0880

AC:

3933

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.190

AC:

4959

AN:

26108

East Asian (EAS)

AF:

0.161

AC:

6397

AN:

39660

South Asian (SAS)

AF:

0.127

AC:

10929

AN:

86224

European-Finnish (FIN)

AF:

0.125

AC:

6680

AN:

53374

Middle Eastern (MID)

AF:

0.199

AC:

1149

AN:

5764

European-Non Finnish (NFE)

AF:

0.168

AC:

187013

AN:

1110374

Other (OTH)

AF:

0.162

AC:

9787

AN:

60308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.434

Heterozygous variant carriers

10637

21275

31912

42550

53187

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6644

13288

19932

26576

33220

<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:

0.151

AC:

23008

AN:

152264

Hom.:

1762

Cov.:

AF XY:

0.148

AC XY:

11011

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.134

AC:

5555

AN:

41544

American (AMR)

AF:

0.125

AC:

1919

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.194

AC:

673

AN:

3470

East Asian (EAS)

AF:

0.196

AC:

1017

AN:

5176

South Asian (SAS)

AF:

0.122

AC:

590

AN:

4830

European-Finnish (FIN)

AF:

0.128

AC:

1362

AN:

10606

Middle Eastern (MID)

AF:

0.178

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.168

AC:

11444

AN:

68018

Other (OTH)

AF:

0.170

AC:

360

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1038

2075

3113

4150

5188

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

262

524

786

1048

1310

<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:

0.161

Hom.:

6166

Bravo

AF:

0.152

TwinsUK

AF:

0.182

AC:

675

ALSPAC

AF:

0.165

AC:

634

ESP6500AA

AF:

0.126

AC:

469

ESP6500EA

AF:

0.169

AC:

1393

ExAC

AF:

0.149

AC:

17988

Asia WGS

AF:

0.129

AC:

449

AN:

3478

EpiCase

AF:

0.176

EpiControl

AF:

0.177

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

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

Gln639Arg in exon 11 of DNAH11: This variant is not expected to have clinical si gnificance because it has been identified in 16.9% (1393/8222) of European Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs12670130). -

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

Jan 21, 2019

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

Jul 30, 2021

Genome-Nilou Lab

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

0.063

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

8.8

(source)

DANN

Benign

0.23

DEOGEN2

Benign

0.042

.;.;T

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.36

T;T;T

MetaRNN

Benign

0.0027

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.15

.;.;N

PhyloP100

1.9

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.97

.;N;.

REVEL

Benign

0.14

Sift

Benign

0.72

.;T;.

Polyphen

0.0

.;.;B

Vest4

0.012

ClinPred

0.00042

GERP RS

0.13

Varity_R

0.045

gMVP

0.16

Mutation Taster

=98/2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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