rs10269582

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.3068T>C(p.Val1023Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 1,613,428 control chromosomes in the GnomAD database, including 136,336 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 10179 hom., cov: 31)

Exomes 𝑓: 0.41 ( 126157 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.927

Publications

21 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=0.002362281).

BP6

Variant 7-21600743-T-C is Benign according to our data. Variant chr7-21600743-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 178725.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.3068T>C	p.Val1023Ala	missense_variant	Exon 16 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.3068T>C	p.Val1023Ala	missense_variant	Exon 16 of 82	5	NM_001277115.2	ENSP00000475939.1

Frequencies

GnomAD3 genomes

AF:

0.339

AC:

51479

AN:

151782

Hom.:

10176

Cov.:

show subpopulations

Gnomad AFR

AF:

0.172

Gnomad AMI

AF:

0.590

Gnomad AMR

AF:

0.331

Gnomad ASJ

AF:

0.416

Gnomad EAS

AF:

0.0203

Gnomad SAS

AF:

0.249

Gnomad FIN

AF:

0.466

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.446

Gnomad OTH

AF:

0.351

GnomAD2 exomes

AF:

0.354

AC:

88106

AN:

248644

AF XY:

0.356

show subpopulations

Gnomad AFR exome

AF:

0.164

Gnomad AMR exome

AF:

0.324

Gnomad ASJ exome

AF:

0.402

Gnomad EAS exome

AF:

0.0125

Gnomad FIN exome

AF:

0.464

Gnomad NFE exome

AF:

0.442

Gnomad OTH exome

AF:

0.400

GnomAD4 exome

AF:

0.405

AC:

592415

AN:

1461528

Hom.:

126157

Cov.:

AF XY:

0.403

AC XY:

292987

AN XY:

727048

show subpopulations

African (AFR)

AF:

0.163

AC:

5465

AN:

33472

American (AMR)

AF:

0.325

AC:

14514

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.403

AC:

10538

AN:

26132

East Asian (EAS)

AF:

0.0267

AC:

1061

AN:

39694

South Asian (SAS)

AF:

0.265

AC:

22815

AN:

86242

European-Finnish (FIN)

AF:

0.468

AC:

24977

AN:

53402

Middle Eastern (MID)

AF:

0.333

AC:

1918

AN:

5764

European-Non Finnish (NFE)

AF:

0.439

AC:

488107

AN:

1111738

Other (OTH)

AF:

0.381

AC:

23020

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

19673

39346

59020

78693

98366

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14280

28560

42840

57120

71400

<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:

0.339

AC:

51493

AN:

151900

Hom.:

10179

Cov.:

AF XY:

0.334

AC XY:

24814

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.172

AC:

7114

AN:

41458

American (AMR)

AF:

0.331

AC:

5053

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.416

AC:

1443

AN:

3466

East Asian (EAS)

AF:

0.0203

AC:

105

AN:

5170

South Asian (SAS)

AF:

0.249

AC:

1194

AN:

4798

European-Finnish (FIN)

AF:

0.466

AC:

4917

AN:

10554

Middle Eastern (MID)

AF:

0.371

AC:

109

AN:

294

European-Non Finnish (NFE)

AF:

0.446

AC:

30277

AN:

67898

Other (OTH)

AF:

0.353

AC:

744

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1576

3152

4728

6304

7880

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

492

984

1476

1968

2460

<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:

0.403

Hom.:

59431

Bravo

AF:

0.323

TwinsUK

AF:

0.425

AC:

1577

ALSPAC

AF:

0.447

AC:

1722

ESP6500AA

AF:

0.178

AC:

703

ESP6500EA

AF:

0.434

AC:

3630

ExAC

AF:

0.352

AC:

42605

Asia WGS

AF:

0.195

AC:

678

AN:

3478

EpiCase

AF:

0.441

EpiControl

AF:

0.435

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

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Val1023Ala in exon 16 of DNAH11: This variant is not expected to have clinical s ignificance because it has been identified in 43.4% (3630/8356) of European Amer ican chromosomes from a broad population by the NHLBI Exome Sequencing Project ( http://evs.gs.washington.edu/EVS; dbSNP rs10269582). -

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: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

This variant is associated with the following publications: (PMID: 12142464) -

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

0.14

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.21

DEOGEN2

Benign

0.056

.;.;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.53

T;T;T

MetaRNN

Benign

0.0024

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.1

.;.;L

PhyloP100

0.93

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.7

.;N;.

REVEL

Benign

0.061

Sift

Benign

1.0

.;T;.

Polyphen

0.029

.;.;B

Vest4

0.055

ClinPred

0.0070

GERP RS

4.5

Varity_R

0.058

gMVP

0.40

Mutation Taster

=91/9

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