rs2214326

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.10399G>A(p.Ala3467Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 1,611,438 control chromosomes in the GnomAD database, including 114,914 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3467S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.39 ( 12169 hom., cov: 31)

Exomes 𝑓: 0.36 ( 102745 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.144

Publications

26 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:

LOC124901599 (HGNC:):

LOC124901599 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=2.241899E-6).

BP6

Variant 7-21816533-G-A is Benign according to our data. Variant chr7-21816533-G-A is described in ClinVar as Benign. ClinVar VariationId is 178732.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.10399G>A	p.Ala3467Thr	missense_variant	Exon 64 of 82	ENST00000409508.8	NP_001264044.1	Q96DT5Q96NT7H9NAJ8H9NAJ7
LOC124901599	XR_007060248.1 link	n.-63C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8 link	c.10399G>A	p.Ala3467Thr	missense_variant	Exon 64 of 82	5	NM_001277115.2	ENSP00000475939.1		Q96DT5

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58785

AN:

151738

Hom.:

12156

Cov.:

show subpopulations

Gnomad AFR

AF:

0.392

Gnomad AMI

AF:

0.313

Gnomad AMR

AF:

0.481

Gnomad ASJ

AF:

0.267

Gnomad EAS

AF:

0.818

Gnomad SAS

AF:

0.428

Gnomad FIN

AF:

0.363

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.338

Gnomad OTH

AF:

0.389

GnomAD2 exomes

AF:

0.420

AC:

103281

AN:

246088

AF XY:

0.412

show subpopulations

Gnomad AFR exome

AF:

0.390

Gnomad AMR exome

AF:

0.559

Gnomad ASJ exome

AF:

0.272

Gnomad EAS exome

AF:

0.822

Gnomad FIN exome

AF:

0.361

Gnomad NFE exome

AF:

0.341

Gnomad OTH exome

AF:

0.394

GnomAD4 exome

AF:

0.363

AC:

530277

AN:

1459582

Hom.:

102745

Cov.:

AF XY:

0.364

AC XY:

264150

AN XY:

725854

show subpopulations

African (AFR)

AF:

0.395

AC:

13198

AN:

33448

American (AMR)

AF:

0.546

AC:

24204

AN:

44322

Ashkenazi Jewish (ASJ)

AF:

0.278

AC:

7248

AN:

26088

East Asian (EAS)

AF:

0.823

AC:

32604

AN:

39628

South Asian (SAS)

AF:

0.424

AC:

36362

AN:

85794

European-Finnish (FIN)

AF:

0.356

AC:

18987

AN:

53326

Middle Eastern (MID)

AF:

0.422

AC:

2433

AN:

5766

European-Non Finnish (NFE)

AF:

0.335

AC:

372441

AN:

1110902

Other (OTH)

AF:

0.378

AC:

22800

AN:

60308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

18712

37424

56136

74848

93560

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12246

24492

36738

48984

61230

<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:

0.387

AC:

58840

AN:

151856

Hom.:

12169

Cov.:

AF XY:

0.395

AC XY:

29310

AN XY:

74202

show subpopulations

African (AFR)

AF:

0.393

AC:

16240

AN:

41374

American (AMR)

AF:

0.483

AC:

7361

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.267

AC:

926

AN:

3470

East Asian (EAS)

AF:

0.818

AC:

4224

AN:

5164

South Asian (SAS)

AF:

0.427

AC:

2051

AN:

4808

European-Finnish (FIN)

AF:

0.363

AC:

3823

AN:

10530

Middle Eastern (MID)

AF:

0.401

AC:

118

AN:

294

European-Non Finnish (NFE)

AF:

0.338

AC:

22996

AN:

67946

Other (OTH)

AF:

0.387

AC:

818

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1747

3495

5242

6990

8737

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

568

1136

1704

2272

2840

<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:

0.361

Hom.:

47389

Bravo

AF:

0.399

TwinsUK

AF:

0.343

AC:

1270

ALSPAC

AF:

0.357

AC:

1375

ESP6500AA

AF:

0.385

AC:

1532

ESP6500EA

AF:

0.330

AC:

2736

ExAC

AF:

0.409

AC:

49439

Asia WGS

AF:

0.574

AC:

1997

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Jul 18, 2014

Eurofins Ntd Llc (ga)

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

Ala3467Thr in exon 64 of DNAH11: This variant is not expected to have clinical s ignificance because it has been identified in 38.5% (1532/3984) of African Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs2214326). -

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

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

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

0.065

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.013

(source)

DANN

Benign

0.39

DEOGEN2

Benign

0.024

.;.;T

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.073

LIST_S2

Benign

0.54

T;T;T

MetaRNN

Benign

0.0000022

T;T;T

MetaSVM

Benign

-0.93

PhyloP100

-0.14

PrimateAI

Benign

0.23

PROVEAN

Benign

0.83

.;N;.

REVEL

Benign

0.089

Sift

Benign

1.0

.;T;.

Vest4

0.018

ClinPred

0.013

GERP RS

-12

Varity_R

0.055

gMVP

0.096

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