rs6461613

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.12493A>G(p.Met4165Val) variant causes a missense change. The variant allele was found at a frequency of 0.802 in 1,608,656 control chromosomes in the GnomAD database, including 528,502 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

Frequency

Genomes: 𝑓 0.69 ( 39739 hom., cov: 32)

Exomes 𝑓: 0.81 ( 488763 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.69

Publications

28 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=8.890553E-7).

BP6

Variant 7-21884396-A-G is Benign according to our data. Variant chr7-21884396-A-G is described in ClinVar as Benign. ClinVar VariationId is 178735.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.12493A>G	p.Met4165Val	missense_variant	Exon 76 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.12493A>G	p.Met4165Val	missense_variant	Exon 76 of 82	5	NM_001277115.2	ENSP00000475939.1		Q96DT5

Frequencies

GnomAD3 genomes

AF:

0.695

AC:

105726

AN:

152060

Hom.:

39737

Cov.:

show subpopulations

Gnomad AFR

AF:

0.399

Gnomad AMI

AF:

0.903

Gnomad AMR

AF:

0.690

Gnomad ASJ

AF:

0.819

Gnomad EAS

AF:

0.663

Gnomad SAS

AF:

0.743

Gnomad FIN

AF:

0.874

Gnomad MID

AF:

0.778

Gnomad NFE

AF:

0.837

Gnomad OTH

AF:

0.728

GnomAD2 exomes

AF:

0.756

AC:

185702

AN:

245538

AF XY:

0.769

show subpopulations

Gnomad AFR exome

AF:

0.392

Gnomad AMR exome

AF:

0.596

Gnomad ASJ exome

AF:

0.828

Gnomad EAS exome

AF:

0.685

Gnomad FIN exome

AF:

0.862

Gnomad NFE exome

AF:

0.840

Gnomad OTH exome

AF:

0.787

GnomAD4 exome

AF:

0.814

AC:

1185018

AN:

1456478

Hom.:

488763

Cov.:

AF XY:

0.813

AC XY:

589095

AN XY:

724356

show subpopulations

African (AFR)

AF:

0.379

AC:

12629

AN:

33310

American (AMR)

AF:

0.608

AC:

26821

AN:

44082

Ashkenazi Jewish (ASJ)

AF:

0.828

AC:

21540

AN:

26022

East Asian (EAS)

AF:

0.608

AC:

24045

AN:

39526

South Asian (SAS)

AF:

0.749

AC:

63617

AN:

84992

European-Finnish (FIN)

AF:

0.863

AC:

46020

AN:

53324

Middle Eastern (MID)

AF:

0.780

AC:

4476

AN:

5740

European-Non Finnish (NFE)

AF:

0.846

AC:

938105

AN:

1109274

Other (OTH)

AF:

0.793

AC:

47765

AN:

60208

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

9414

18829

28243

37658

47072

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20934

41868

62802

83736

104670

<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:

0.695

AC:

105751

AN:

152178

Hom.:

39739

Cov.:

AF XY:

0.696

AC XY:

51762

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.399

AC:

16570

AN:

41498

American (AMR)

AF:

0.689

AC:

10538

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.819

AC:

2839

AN:

3468

East Asian (EAS)

AF:

0.662

AC:

3422

AN:

5166

South Asian (SAS)

AF:

0.743

AC:

3583

AN:

4822

European-Finnish (FIN)

AF:

0.874

AC:

9256

AN:

10596

Middle Eastern (MID)

AF:

0.776

AC:

228

AN:

294

European-Non Finnish (NFE)

AF:

0.837

AC:

56959

AN:

68018

Other (OTH)

AF:

0.728

AC:

1536

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1356

2712

4067

5423

6779

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

802

1604

2406

3208

4010

<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:

0.779

Hom.:

22253

Bravo

AF:

0.666

TwinsUK

AF:

0.854

AC:

3168

ALSPAC

AF:

0.848

AC:

3270

ESP6500AA

AF:

0.440

AC:

1752

ESP6500EA

AF:

0.848

AC:

7150

ExAC

AF:

0.755

AC:

91244

Asia WGS

AF:

0.673

AC:

2342

AN:

3478

EpiCase

AF:

0.841

EpiControl

AF:

0.839

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Met4165Val in exon 76 of DNAH11: This variant is not expected to have clinical s ignificance because it has been identified in 44.0% (1752/3986) of African Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs6461613). -

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

- -

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: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

- -

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

0.096

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.11

.;.;T

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.59

T;T;T

MetaRNN

Benign

8.9e-7

T;T;T

MetaSVM

Benign

-1.1

PhyloP100

3.7

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.5

.;N;.

REVEL

Benign

0.11

Sift

Benign

0.14

.;T;.

Vest4

0.11

ClinPred

0.027

GERP RS

5.7

Varity_R

0.65

gMVP

0.37

Mutation Taster

=99/1

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