rs72655982

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001277115.2(DNAH11):c.1199C>T(p.Thr400Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0448 in 1,597,816 control chromosomes in the GnomAD database, including 1,819 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 139 hom., cov: 32)

Exomes 𝑓: 0.045 ( 1680 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.762

Publications

12 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:

LOC105375183 (HGNC:):

LOC105375183 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 7-21570073-C-T is Benign according to our data. Variant chr7-21570073-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 163095.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.1199C>T	p.Thr400Ile	missense_variant	Exon 7 of 82	ENST00000409508.8	NP_001264044.1	Q96DT5Q96NT7H9NAJ8H9NAJ7
LOC105375183	XR_007060247.1 link	n.282+3253G>A		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8 link	c.1199C>T	p.Thr400Ile	missense_variant	Exon 7 of 82	5	NM_001277115.2	ENSP00000475939.1		Q96DT5
DNAH11	ENST00000496218.1 link	n.85C>T		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0409

AC:

6217

AN:

152120

Hom.:

139

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0409

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0206

Gnomad ASJ

AF:

0.0421

Gnomad EAS

AF:

0.0201

Gnomad SAS

AF:

0.0623

Gnomad FIN

AF:

0.0365

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0464

Gnomad OTH

AF:

0.0397

GnomAD2 exomes

AF:

0.0395

AC:

9028

AN:

228282

AF XY:

0.0413

show subpopulations

Gnomad AFR exome

AF:

0.0379

Gnomad AMR exome

AF:

0.0130

Gnomad ASJ exome

AF:

0.0468

Gnomad EAS exome

AF:

0.0241

Gnomad FIN exome

AF:

0.0351

Gnomad NFE exome

AF:

0.0467

Gnomad OTH exome

AF:

0.0362

GnomAD4 exome

AF:

0.0452

AC:

65374

AN:

1445578

Hom.:

1680

Cov.:

AF XY:

0.0456

AC XY:

32710

AN XY:

717892

show subpopulations

African (AFR)

AF:

0.0422

AC:

1385

AN:

32852

American (AMR)

AF:

0.0143

AC:

604

AN:

42152

Ashkenazi Jewish (ASJ)

AF:

0.0447

AC:

1145

AN:

25638

East Asian (EAS)

AF:

0.0131

AC:

515

AN:

39346

South Asian (SAS)

AF:

0.0560

AC:

4656

AN:

83112

European-Finnish (FIN)

AF:

0.0374

AC:

1972

AN:

52794

Middle Eastern (MID)

AF:

0.0379

AC:

216

AN:

5698

European-Non Finnish (NFE)

AF:

0.0474

AC:

52322

AN:

1104230

Other (OTH)

AF:

0.0428

AC:

2559

AN:

59756

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

2606

5212

7817

10423

13029

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1978

3956

5934

7912

9890

<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:

0.0408

AC:

6215

AN:

152238

Hom.:

139

Cov.:

AF XY:

0.0403

AC XY:

3001

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0407

AC:

1693

AN:

41548

American (AMR)

AF:

0.0205

AC:

313

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0421

AC:

146

AN:

3472

East Asian (EAS)

AF:

0.0201

AC:

104

AN:

5174

South Asian (SAS)

AF:

0.0626

AC:

302

AN:

4824

European-Finnish (FIN)

AF:

0.0365

AC:

387

AN:

10604

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0464

AC:

3152

AN:

68000

Other (OTH)

AF:

0.0393

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

300

600

900

1200

1500

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<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:

0.0448

Hom.:

513

Bravo

AF:

0.0384

TwinsUK

AF:

0.0515

AC:

191

ALSPAC

AF:

0.0483

AC:

186

ESP6500AA

AF:

0.0407

AC:

150

ESP6500EA

AF:

0.0441

AC:

360

ExAC

AF:

0.0394

AC:

4748

Asia WGS

AF:

0.0410

AC:

143

AN:

3476

ClinVar

Significance: Benign/Likely 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

Thr400Ile in exon 7 of DNAH11: This variant is not expected to have clinical sig nificance because it has been identified in 4.4% (360/8170) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs72655982). -

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:Likely 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

- -

not provided

Benign:2

Dec 31, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.33

(source)

DANN

Benign

0.30

DEOGEN2

Benign

0.11

.;.;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.020

T;T;T

MetaRNN

Benign

0.0024

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

.;.;N

PhyloP100

-0.76

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.4

.;N;.

REVEL

Benign

0.037

Sift

Benign

0.49

.;T;.

Polyphen

0.0

.;.;B

Vest4

0.037

ClinPred

0.00038

GERP RS

-5.2

Varity_R

0.047

gMVP

0.066

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.28

Position offset: -4

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