rs2285942

Variant names:

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.54C>T(p.Thr18Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,548,618 control chromosomes in the GnomAD database, including 14,802 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.099 ( 932 hom., cov: 33)

Exomes 𝑓: 0.14 ( 13870 hom. )

Consequence

DNAH11
NM_001277115.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.521

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: 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=-0.64).

BP6

Variant 7-21543299-C-T is Benign according to our data. Variant chr7-21543299-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 178721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.521 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.54C>T	p.Thr18Thr	synonymous_variant	Exon 1 of 82	ENST00000409508.8	NP_001264044.1	Q96DT5Q96NT7H9NAJ8H9NAJ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8 link	c.54C>T	p.Thr18Thr	synonymous_variant	Exon 1 of 82	5	NM_001277115.2	ENSP00000475939.1		Q96DT5
DNAH11	ENST00000607050.1 link	n.-147C>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0986

AC:

14999

AN:

152088

Hom.:

932

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0326

Gnomad AMI

AF:

0.0833

Gnomad AMR

AF:

0.0846

Gnomad ASJ

AF:

0.0766

Gnomad EAS

AF:

0.0561

Gnomad SAS

AF:

0.0589

Gnomad FIN

AF:

0.135

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.144

Gnomad OTH

AF:

0.0984

GnomAD2 exomes

AF:

0.100

AC:

15074

AN:

150352

AF XY:

0.101

show subpopulations

Gnomad AFR exome

AF:

0.0261

Gnomad AMR exome

AF:

0.0596

Gnomad ASJ exome

AF:

0.0843

Gnomad EAS exome

AF:

0.0439

Gnomad FIN exome

AF:

0.144

Gnomad NFE exome

AF:

0.144

Gnomad OTH exome

AF:

0.0996

GnomAD4 exome

AF:

0.136

AC:

189940

AN:

1396412

Hom.:

13870

Cov.:

AF XY:

0.134

AC XY:

92020

AN XY:

688484

show subpopulations

African (AFR)

AF:

0.0268

AC:

845

AN:

31532

American (AMR)

AF:

0.0664

AC:

2367

AN:

35654

Ashkenazi Jewish (ASJ)

AF:

0.0873

AC:

2195

AN:

25142

East Asian (EAS)

AF:

0.0779

AC:

2781

AN:

35702

South Asian (SAS)

AF:

0.0650

AC:

5147

AN:

79140

European-Finnish (FIN)

AF:

0.146

AC:

7064

AN:

48444

Middle Eastern (MID)

AF:

0.0638

AC:

316

AN:

4952

European-Non Finnish (NFE)

AF:

0.151

AC:

162273

AN:

1077982

Other (OTH)

AF:

0.120

AC:

6952

AN:

57864

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

11131

22262

33393

44524

55655

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5804

11608

17412

23216

29020

<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:

0.0985

AC:

14998

AN:

152206

Hom.:

932

Cov.:

AF XY:

0.0955

AC XY:

7108

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0326

AC:

1357

AN:

41564

American (AMR)

AF:

0.0844

AC:

1291

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0766

AC:

266

AN:

3472

East Asian (EAS)

AF:

0.0564

AC:

290

AN:

5142

South Asian (SAS)

AF:

0.0585

AC:

282

AN:

4820

European-Finnish (FIN)

AF:

0.135

AC:

1428

AN:

10612

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.144

AC:

9786

AN:

67970

Other (OTH)

AF:

0.0974

AC:

206

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

681

1362

2042

2723

3404

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

178

356

534

712

890

<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:

0.130

Hom.:

3365

Bravo

AF:

0.0917

Asia WGS

AF:

0.0520

AC:

180

AN:

3478

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

Thr18Thr in exon 1 of DNAH11: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 10.9% (715/6530) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2285942). -

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

Nov 27, 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

BayesDel_noAF

Benign

-0.64

CADD

Benign

3.7

(source)

DANN

Benign

0.92

PhyloP100

-0.52

PromoterAI

0.017

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