rs2072221

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001277115.2(DNAH11):c.7626G>A(p.Thr2542Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.855 in 1,610,410 control chromosomes in the GnomAD database, including 592,010 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T2542T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.83 ( 53172 hom., cov: 32)

Exomes 𝑓: 0.86 ( 538838 hom. )

Consequence

DNAH11
NM_001277115.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.496

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 7-21735825-G-A is Benign according to our data. Variant chr7-21735825-G-A is described in ClinVar as Benign. ClinVar VariationId is 163110.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.496 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.7626G>A	p.Thr2542Thr	synonymous_variant	Exon 46 of 82	ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8 link	c.7626G>A	p.Thr2542Thr	synonymous_variant	Exon 46 of 82	5	NM_001277115.2	ENSP00000475939.1
DNAH11	ENST00000605912.1 link	c.186G>A	p.Thr62Thr	synonymous_variant	Exon 1 of 4	3		ENSP00000476068.1

Frequencies

GnomAD3 genomes

AF:

0.833

AC:

126621

AN:

152026

Hom.:

53154

Cov.:

show subpopulations

Gnomad AFR

AF:

0.795

Gnomad AMI

AF:

0.863

Gnomad AMR

AF:

0.868

Gnomad ASJ

AF:

0.769

Gnomad EAS

AF:

0.527

Gnomad SAS

AF:

0.761

Gnomad FIN

AF:

0.904

Gnomad MID

AF:

0.797

Gnomad NFE

AF:

0.869

Gnomad OTH

AF:

0.817

GnomAD2 exomes

AF:

0.825

AC:

204412

AN:

247696

AF XY:

0.827

show subpopulations

Gnomad AFR exome

AF:

0.796

Gnomad AMR exome

AF:

0.865

Gnomad ASJ exome

AF:

0.777

Gnomad EAS exome

AF:

0.519

Gnomad FIN exome

AF:

0.900

Gnomad NFE exome

AF:

0.867

Gnomad OTH exome

AF:

0.828

GnomAD4 exome

AF:

0.857

AC:

1250264

AN:

1458266

Hom.:

538838

Cov.:

AF XY:

0.856

AC XY:

620240

AN XY:

724930

show subpopulations

African (AFR)

AF:

0.794

AC:

26506

AN:

33386

American (AMR)

AF:

0.867

AC:

38652

AN:

44586

Ashkenazi Jewish (ASJ)

AF:

0.775

AC:

20183

AN:

26044

East Asian (EAS)

AF:

0.566

AC:

22428

AN:

39624

South Asian (SAS)

AF:

0.790

AC:

67727

AN:

85732

European-Finnish (FIN)

AF:

0.897

AC:

47786

AN:

53298

Middle Eastern (MID)

AF:

0.771

AC:

4434

AN:

5752

European-Non Finnish (NFE)

AF:

0.877

AC:

972675

AN:

1109624

Other (OTH)

AF:

0.828

AC:

49873

AN:

60220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

8337

16673

25010

33346

41683

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21264

42528

63792

85056

106320

<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:

0.833

AC:

126695

AN:

152144

Hom.:

53172

Cov.:

AF XY:

0.832

AC XY:

61855

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.795

AC:

32988

AN:

41494

American (AMR)

AF:

0.868

AC:

13264

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.769

AC:

2671

AN:

3472

East Asian (EAS)

AF:

0.527

AC:

2718

AN:

5156

South Asian (SAS)

AF:

0.760

AC:

3662

AN:

4816

European-Finnish (FIN)

AF:

0.904

AC:

9571

AN:

10586

Middle Eastern (MID)

AF:

0.789

AC:

232

AN:

294

European-Non Finnish (NFE)

AF:

0.869

AC:

59082

AN:

68016

Other (OTH)

AF:

0.815

AC:

1722

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1047

2094

3142

4189

5236

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

878

1756

2634

3512

4390

<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:

0.854

Hom.:

143290

Bravo

AF:

0.839

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

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

Thr2542Thr in exon 46 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 15.2% (589/3870) of African American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2072221). -

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 28, 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

-0.67

CADD

Benign

0.13

(source)

DANN

Benign

0.43

PhyloP100

-0.50

PromoterAI

-0.019

Neutral

(source)

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