rs72655988

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.1702G>A(p.Ala568Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0442 in 1,603,644 control chromosomes in the GnomAD database, including 1,805 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 134 hom., cov: 33)

Exomes 𝑓: 0.045 ( 1671 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.48

Publications

14 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: Labcorp Genetics (formerly Invitae), ClinGen, Laboratory for Molecular Medicine
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=0.0040915906).

BP6

Variant 7-21582013-G-A is Benign according to our data. Variant chr7-21582013-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 178724.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0562 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277115.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	NM_001277115.2	MANE Select	c.1702G>A	p.Ala568Thr	missense	Exon 9 of 82	NP_001264044.1	Q96DT5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.1702G>A	p.Ala568Thr	missense	Exon 9 of 82	ENSP00000475939.1	Q96DT5

Frequencies

GnomAD3 genomes

AF:

0.0406

AC:

6171

AN:

152154

Hom.:

134

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0408

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.0204

Gnomad ASJ

AF:

0.0421

Gnomad EAS

AF:

0.0187

Gnomad SAS

AF:

0.0617

Gnomad FIN

AF:

0.0364

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0459

Gnomad OTH

AF:

0.0398

GnomAD2 exomes

AF:

0.0395

AC:

9788

AN:

247902

AF XY:

0.0411

show subpopulations

Gnomad AFR exome

AF:

0.0390

Gnomad AMR exome

AF:

0.0121

Gnomad ASJ exome

AF:

0.0462

Gnomad EAS exome

AF:

0.0236

Gnomad FIN exome

AF:

0.0350

Gnomad NFE exome

AF:

0.0469

Gnomad OTH exome

AF:

0.0376

GnomAD4 exome

AF:

0.0446

AC:

64676

AN:

1451372

Hom.:

1671

Cov.:

AF XY:

0.0450

AC XY:

32494

AN XY:

722518

show subpopulations

African (AFR)

AF:

0.0415

AC:

1382

AN:

33270

American (AMR)

AF:

0.0135

AC:

603

AN:

44646

Ashkenazi Jewish (ASJ)

AF:

0.0445

AC:

1158

AN:

26042

East Asian (EAS)

AF:

0.0126

AC:

499

AN:

39652

South Asian (SAS)

AF:

0.0550

AC:

4720

AN:

85880

European-Finnish (FIN)

AF:

0.0374

AC:

1988

AN:

53146

Middle Eastern (MID)

AF:

0.0379

AC:

215

AN:

5674

European-Non Finnish (NFE)

AF:

0.0468

AC:

51568

AN:

1103030

Other (OTH)

AF:

0.0424

AC:

2543

AN:

60032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

2571

5142

7713

10284

12855

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1930

3860

5790

7720

9650

<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:

0.0405

AC:

6169

AN:

152272

Hom.:

134

Cov.:

AF XY:

0.0399

AC XY:

2974

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0406

AC:

1689

AN:

41552

American (AMR)

AF:

0.0203

AC:

311

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0421

AC:

146

AN:

3470

East Asian (EAS)

AF:

0.0187

AC:

AN:

5182

South Asian (SAS)

AF:

0.0620

AC:

299

AN:

4826

European-Finnish (FIN)

AF:

0.0364

AC:

387

AN:

10624

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0459

AC:

3123

AN:

68018

Other (OTH)

AF:

0.0394

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

307

614

920

1227

1534

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:

0.0435

Hom.:

462

Bravo

AF:

0.0381

TwinsUK

AF:

0.0515

AC:

191

ALSPAC

AF:

0.0485

AC:

187

ESP6500AA

AF:

0.0401

AC:

145

ESP6500EA

AF:

0.0444

AC:

362

ExAC

AF:

0.0413

AC:

4984

Asia WGS

AF:

0.0410

AC:

142

AN:

3478

EpiCase

AF:

0.0410

EpiControl

AF:

0.0409

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Primary ciliary dyskinesia (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

0.10

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.82

MetaRNN

Benign

0.0041

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

PhyloP100

2.5

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.3

REVEL

Benign

0.13

Sift

Benign

0.28

Polyphen

0.031

Vest4

0.12

ClinPred

0.026

GERP RS

5.9

Varity_R

0.30

gMVP

0.23

Mutation Taster

=84/16

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over