7-21861948-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001277115.2(DNAH11):c.11298T>C(p.His3766His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 1,613,306 control chromosomes in the GnomAD database, including 496,202 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 40341 hom., cov: 30)

Exomes 𝑓: 0.79 ( 455861 hom. )

Consequence

DNAH11
NM_001277115.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -2.36

Publications

19 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.135).

BP6

Variant 7-21861948-T-C is Benign according to our data. Variant chr7-21861948-T-C is described in ClinVar as Benign. ClinVar VariationId is 163126.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.36 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.11298T>C	p.His3766His	synonymous_variant	Exon 69 of 82	ENST00000409508.8	NP_001264044.1	Q96DT5Q96NT7H9NAJ8H9NAJ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH11	ENST00000409508.8 link	c.11298T>C	p.His3766His	synonymous_variant	Exon 69 of 82	5	NM_001277115.2	ENSP00000475939.1	Q96DT5
DNAH11	ENST00000421290.1 link	n.481T>C		non_coding_transcript_exon_variant	Exon 4 of 4	4
DNAH11	ENST00000607413.5 link	n.561T>C		non_coding_transcript_exon_variant	Exon 4 of 4	4

Frequencies

GnomAD3 genomes

AF:

0.720

AC:

109280

AN:

151842

Hom.:

40296

Cov.:

show subpopulations

Gnomad AFR

AF:

0.590

Gnomad AMI

AF:

0.877

Gnomad AMR

AF:

0.655

Gnomad ASJ

AF:

0.827

Gnomad EAS

AF:

0.543

Gnomad SAS

AF:

0.662

Gnomad FIN

AF:

0.771

Gnomad MID

AF:

0.741

Gnomad NFE

AF:

0.814

Gnomad OTH

AF:

0.744

GnomAD2 exomes

AF:

0.721

AC:

179230

AN:

248552

AF XY:

0.731

show subpopulations

Gnomad AFR exome

AF:

0.586

Gnomad AMR exome

AF:

0.569

Gnomad ASJ exome

AF:

0.816

Gnomad EAS exome

AF:

0.541

Gnomad FIN exome

AF:

0.760

Gnomad NFE exome

AF:

0.811

Gnomad OTH exome

AF:

0.752

GnomAD4 exome

AF:

0.786

AC:

1148072

AN:

1461346

Hom.:

455861

Cov.:

AF XY:

0.784

AC XY:

569803

AN XY:

726950

show subpopulations

African (AFR)

AF:

0.587

AC:

19630

AN:

33462

American (AMR)

AF:

0.580

AC:

25937

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.813

AC:

21256

AN:

26134

East Asian (EAS)

AF:

0.536

AC:

21273

AN:

39674

South Asian (SAS)

AF:

0.674

AC:

58057

AN:

86174

European-Finnish (FIN)

AF:

0.761

AC:

40628

AN:

53372

Middle Eastern (MID)

AF:

0.757

AC:

4359

AN:

5760

European-Non Finnish (NFE)

AF:

0.819

AC:

910463

AN:

1111724

Other (OTH)

AF:

0.770

AC:

46469

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

12759

25517

38276

51034

63793

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20812

41624

62436

83248

104060

<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:

0.720

AC:

109375

AN:

151960

Hom.:

40341

Cov.:

AF XY:

0.716

AC XY:

53141

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.591

AC:

24472

AN:

41420

American (AMR)

AF:

0.654

AC:

9997

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.827

AC:

2868

AN:

3468

East Asian (EAS)

AF:

0.542

AC:

2793

AN:

5152

South Asian (SAS)

AF:

0.662

AC:

3179

AN:

4800

European-Finnish (FIN)

AF:

0.771

AC:

8130

AN:

10542

Middle Eastern (MID)

AF:

0.738

AC:

217

AN:

294

European-Non Finnish (NFE)

AF:

0.814

AC:

55345

AN:

67978

Other (OTH)

AF:

0.745

AC:

1574

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1456

2912

4369

5825

7281

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

832

1664

2496

3328

4160

<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:

0.774

Hom.:

150638

Bravo

AF:

0.705

Asia WGS

AF:

0.615

AC:

2140

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

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

His3766His in exon 69 of DNAH11: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 38.0% (1553/4084) of African American chromosomes from a broad population by the NHLBI Exome Sequ encing Project (http://evs.gs.washington.edu/EVS; dbSNP rs4722067). -

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

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.0070

(source)

DANN

Benign

0.29

PhyloP100

-2.4

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