chr7-21543346-A-T

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.101A>T(p.Glu34Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 1,550,724 control chromosomes in the GnomAD database, including 181,836 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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. E34L) has been classified as Benign.

Frequency

Genomes: 𝑓 0.45 ( 15491 hom., cov: 34)

Exomes 𝑓: 0.48 ( 166345 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.369

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=3.2663345E-4).

BP6

Variant 7-21543346-A-T is Benign according to our data. Variant chr7-21543346-A-T is described in CliVar as Benign. Clinvar id is 93683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21543346-A-T is described in CliVar as Benign. Clinvar id is 93683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.101A>T	p.Glu34Val	missense_variant	Exon 1 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.101A>T	p.Glu34Val	missense_variant	Exon 1 of 82	5	NM_001277115.2	ENSP00000475939.1		Q96DT5
DNAH11	ENST00000607050.1 link	n.-100A>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.447

AC:

67793

AN:

151720

Hom.:

15472

Cov.:

show subpopulations

Gnomad AFR

AF:

0.425

Gnomad AMI

AF:

0.323

Gnomad AMR

AF:

0.364

Gnomad ASJ

AF:

0.482

Gnomad EAS

AF:

0.260

Gnomad SAS

AF:

0.493

Gnomad FIN

AF:

0.414

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.494

Gnomad OTH

AF:

0.465

GnomAD2 exomes

AF:

0.437

AC:

66886

AN:

152884

AF XY:

0.449

show subpopulations

Gnomad AFR exome

AF:

0.432

Gnomad AMR exome

AF:

0.307

Gnomad ASJ exome

AF:

0.494

Gnomad EAS exome

AF:

0.250

Gnomad FIN exome

AF:

0.426

Gnomad NFE exome

AF:

0.494

Gnomad OTH exome

AF:

0.448

GnomAD4 exome

AF:

0.485

AC:

678031

AN:

1398886

Hom.:

166345

Cov.:

AF XY:

0.486

AC XY:

335054

AN XY:

689954

show subpopulations

African (AFR)

AF:

0.429

AC:

13550

AN:

31588

American (AMR)

AF:

0.326

AC:

11624

AN:

35688

Ashkenazi Jewish (ASJ)

AF:

0.493

AC:

12419

AN:

25168

East Asian (EAS)

AF:

0.300

AC:

10737

AN:

35732

South Asian (SAS)

AF:

0.509

AC:

40296

AN:

79216

European-Finnish (FIN)

AF:

0.430

AC:

21105

AN:

49074

Middle Eastern (MID)

AF:

0.552

AC:

3089

AN:

5592

European-Non Finnish (NFE)

AF:

0.499

AC:

537980

AN:

1078832

Other (OTH)

AF:

0.470

AC:

27231

AN:

57996

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

23633

47266

70899

94532

118165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15928

31856

47784

63712

79640

<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:

0.447

AC:

67846

AN:

151838

Hom.:

15491

Cov.:

AF XY:

0.442

AC XY:

32813

AN XY:

74214

show subpopulations

African (AFR)

AF:

0.425

AC:

17622

AN:

41418

American (AMR)

AF:

0.363

AC:

5540

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.482

AC:

1674

AN:

3470

East Asian (EAS)

AF:

0.261

AC:

1340

AN:

5132

South Asian (SAS)

AF:

0.495

AC:

2378

AN:

4806

European-Finnish (FIN)

AF:

0.414

AC:

4363

AN:

10546

Middle Eastern (MID)

AF:

0.531

AC:

156

AN:

294

European-Non Finnish (NFE)

AF:

0.494

AC:

33508

AN:

67882

Other (OTH)

AF:

0.461

AC:

972

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1992

3984

5976

7968

9960

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

642

1284

1926

2568

3210

<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:

0.482

Hom.:

5716

Bravo

AF:

0.441

TwinsUK

AF:

0.495

AC:

1835

ALSPAC

AF:

0.491

AC:

1892

ESP6500AA

AF:

0.380

AC:

1320

ESP6500EA

AF:

0.451

AC:

3331

ExAC

AF:

0.325

AC:

18950

Asia WGS

AF:

0.334

AC:

1161

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

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

Glu34Val in exon 1 of DNAH11: This variant is not expected to have clinical sign ificance because it has been identified in 45.1% (3331/7390) of European America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs2285944). -

Oct 28, 2013

Eurofins Ntd Llc (ga)

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 04, 2024

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

0.11

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.029

.;.;T

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.61

T;T;T

MetaRNN

Benign

0.00033

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.0

.;.;L

PhyloP100

0.37

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.3

.;N;.

REVEL

Benign

0.081

Sift

Uncertain

0.027

.;D;.

Polyphen

0.86

.;.;P

Vest4

0.12

ClinPred

0.0083

GERP RS

2.3

PromoterAI

-0.019

Neutral

(source)

Varity_R

0.39

gMVP

0.57

Mutation Taster

=96/4

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