NM_001277115.2:c.12943G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001277115.2(DNAH11):c.12943G>A(p.Ala4315Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0322 in 1,613,862 control chromosomes in the GnomAD database, including 1,006 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A4315A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.023 ( 60 hom., cov: 33)

Exomes 𝑓: 0.033 ( 946 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.720

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017455816).

BP6

Variant 7-21894893-G-A is Benign according to our data. Variant chr7-21894893-G-A is described in ClinVar as Benign. ClinVar VariationId is 178738.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0231 (3516/152254) while in subpopulation NFE AF = 0.0364 (2477/68020). AF 95% confidence interval is 0.0352. There are 60 homozygotes in GnomAd4. There are 1635 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 60 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.12943G>A	p.Ala4315Thr	missense_variant	Exon 79 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.12943G>A	p.Ala4315Thr	missense_variant	Exon 79 of 82	5	NM_001277115.2	ENSP00000475939.1
DNAH11	ENST00000479878.1 link	n.314G>A		non_coding_transcript_exon_variant	Exon 2 of 5	3

Frequencies

GnomAD3 genomes

AF:

0.0231

AC:

3519

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00688

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0213

Gnomad ASJ

AF:

0.0389

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0201

Gnomad FIN

AF:

0.0107

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0364

Gnomad OTH

AF:

0.0321

GnomAD2 exomes

AF:

0.0239

AC:

5963

AN:

249198

AF XY:

0.0252

show subpopulations

Gnomad AFR exome

AF:

0.00646

Gnomad AMR exome

AF:

0.0118

Gnomad ASJ exome

AF:

0.0349

Gnomad EAS exome

AF:

0.000167

Gnomad FIN exome

AF:

0.0138

Gnomad NFE exome

AF:

0.0358

Gnomad OTH exome

AF:

0.0319

GnomAD4 exome

AF:

0.0332

AC:

48506

AN:

1461608

Hom.:

946

Cov.:

AF XY:

0.0328

AC XY:

23866

AN XY:

727082

show subpopulations

African (AFR)

AF:

0.00547

AC:

183

AN:

33480

American (AMR)

AF:

0.0127

AC:

568

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0352

AC:

921

AN:

26134

East Asian (EAS)

AF:

0.000126

AC:

AN:

39700

South Asian (SAS)

AF:

0.0195

AC:

1684

AN:

86248

European-Finnish (FIN)

AF:

0.0148

AC:

789

AN:

53402

Middle Eastern (MID)

AF:

0.0371

AC:

214

AN:

5768

European-Non Finnish (NFE)

AF:

0.0382

AC:

42430

AN:

1111786

Other (OTH)

AF:

0.0284

AC:

1712

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

2310

4621

6931

9242

11552

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1614

3228

4842

6456

8070

<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:

0.0231

AC:

3516

AN:

152254

Hom.:

Cov.:

AF XY:

0.0220

AC XY:

1635

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.00686

AC:

285

AN:

41544

American (AMR)

AF:

0.0212

AC:

324

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0389

AC:

135

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.0201

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0107

AC:

114

AN:

10616

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0364

AC:

2477

AN:

68020

Other (OTH)

AF:

0.0317

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

168

336

503

671

839

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.0322

Hom.:

279

Bravo

AF:

0.0234

TwinsUK

AF:

0.0378

AC:

140

ALSPAC

AF:

0.0462

AC:

178

ESP6500AA

AF:

0.00654

AC:

ESP6500EA

AF:

0.0356

AC:

294

ExAC

AF:

0.0238

AC:

2883

Asia WGS

AF:

0.00837

AC:

AN:

3478

EpiCase

AF:

0.0338

EpiControl

AF:

0.0365

ClinVar

Significance: Benign

Submissions summary: Benign:4

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

Ala4315Thr in exon 79 of DNAH11: This variant is not expected to have clinical s ignificance because it has been identified in 3.6% (294/8262) of European Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs72658825). -

Primary ciliary dyskinesia

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Mar 03, 2020

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

0.073

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.0

(source)

DANN

Benign

0.085

DEOGEN2

Benign

0.021

.;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0067

LIST_S2

Benign

0.77

T;T;T

MetaRNN

Benign

0.0017

T;T;T

MetaSVM

Benign

-0.92

PhyloP100

0.72

PrimateAI

Benign

0.22

PROVEAN

Benign

2.5

.;N;.

REVEL

Benign

0.018

Sift

Benign

1.0

.;T;.

Vest4

0.037

ClinPred

0.00087

GERP RS

2.0

Varity_R

0.040

gMVP

0.11

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