7-21852629-A-G

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.11059A>G(p.Lys3687Glu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00218 in 1,582,704 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 41 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 30 hom. )

Consequence

DNAH11
NM_001277115.2 missense, splice_region

Scores

Splicing: ADA: 0.009570

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 5.24

Publications

3 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=0.008550942).

BP6

Variant 7-21852629-A-G is Benign according to our data. Variant chr7-21852629-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0114 (1737/152266) while in subpopulation AFR AF = 0.0391 (1623/41550). AF 95% confidence interval is 0.0375. There are 41 homozygotes in GnomAd4. There are 805 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 41 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.11059A>G	p.Lys3687Glu	missense_variant, splice_region_variant	Exon 67 of 82	ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
DNAH11	ENST00000409508.8 link	c.11059A>G	p.Lys3687Glu	missense_variant, splice_region_variant	Exon 67 of 82	5	NM_001277115.2	ENSP00000475939.1
DNAH11	ENST00000421290.1 link	n.242A>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 4	4
DNAH11	ENST00000607413.5 link	n.322A>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 4	4

Frequencies

GnomAD3 genomes

AF:

0.0114

AC:

1734

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0391

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00956

GnomAD2 exomes

AF:

0.00340

AC:

751

AN:

220596

AF XY:

0.00266

show subpopulations

Gnomad AFR exome

AF:

0.0427

Gnomad AMR exome

AF:

0.00203

Gnomad ASJ exome

AF:

0.00334

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000135

Gnomad OTH exome

AF:

0.00253

GnomAD4 exome

AF:

0.00120

AC:

1719

AN:

1430438

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

767

AN XY:

709134

show subpopulations

African (AFR)

AF:

0.0418

AC:

1343

AN:

32122

American (AMR)

AF:

0.00253

AC:

AN:

38720

Ashkenazi Jewish (ASJ)

AF:

0.00256

AC:

AN:

24254

East Asian (EAS)

AF:

0.00

AC:

AN:

39402

South Asian (SAS)

AF:

0.0000876

AC:

AN:

79952

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52532

Middle Eastern (MID)

AF:

0.000539

AC:

AN:

5562

European-Non Finnish (NFE)

AF:

0.0000491

AC:

AN:

1098894

Other (OTH)

AF:

0.00258

AC:

152

AN:

59000

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

154

232

309

386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<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:

0.0114

AC:

1737

AN:

152266

Hom.:

Cov.:

AF XY:

0.0108

AC XY:

805

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0391

AC:

1623

AN:

41550

American (AMR)

AF:

0.00471

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68018

Other (OTH)

AF:

0.00946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

156

233

311

389

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00389

Hom.:

Bravo

AF:

0.0130

ESP6500AA

AF:

0.0342

AC:

138

ESP6500EA

AF:

0.000238

AC:

ExAC

AF:

0.00351

AC:

425

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Sep 24, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

See Variant Classification Assertion Criteria.

Aug 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

DNAH11: BP4, BS1, BS2

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Primary ciliary dyskinesia 7

Benign:1

Oct 18, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0

.;.;T

Eigen

Pathogenic

0.81

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

D;D;D

MetaRNN

Benign

0.0086

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;.;.

PhyloP100

5.2

PrimateAI

Benign

0.46

PROVEAN

Benign

0.0

.;D;.

REVEL

Benign

0.0

Sift

Pathogenic

0.0

.;D;.

Sift4G

Pathogenic

0.0

.;.;.

Vest4

0.54

ClinPred

0.098

GERP RS

3.7

Varity_R

0.60

gMVP

0.62

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0096

dbscSNV1_RF

Benign

0.084

SpliceAI score (max)

0.090

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over