chr7-21559615-C-T

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.705C>T(p.Asn235Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 1,593,732 control chromosomes in the GnomAD database, including 158,726 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16846 hom., cov: 32)

Exomes 𝑓: 0.44 ( 141880 hom. )

Consequence

DNAH11
NM_001277115.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.401

Publications

18 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 (BayesDel_noAF=-0.38).

BP6

Variant 7-21559615-C-T is Benign according to our data. Variant chr7-21559615-C-T is described in ClinVar as Benign. ClinVar VariationId is 93693.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.401 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.705C>T	p.Asn235Asn	synonymous_variant	Exon 4 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.705C>T	p.Asn235Asn	synonymous_variant	Exon 4 of 82	5	NM_001277115.2	ENSP00000475939.1		Q96DT5
DNAH11	ENST00000483691.1 link	n.-100C>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.463

AC:

70261

AN:

151730

Hom.:

16817

Cov.:

show subpopulations

Gnomad AFR

AF:

0.541

Gnomad AMI

AF:

0.210

Gnomad AMR

AF:

0.385

Gnomad ASJ

AF:

0.392

Gnomad EAS

AF:

0.749

Gnomad SAS

AF:

0.541

Gnomad FIN

AF:

0.386

Gnomad MID

AF:

0.417

Gnomad NFE

AF:

0.425

Gnomad OTH

AF:

0.456

GnomAD2 exomes

AF:

0.447

AC:

105203

AN:

235568

AF XY:

0.450

show subpopulations

Gnomad AFR exome

AF:

0.533

Gnomad AMR exome

AF:

0.321

Gnomad ASJ exome

AF:

0.406

Gnomad EAS exome

AF:

0.746

Gnomad FIN exome

AF:

0.386

Gnomad NFE exome

AF:

0.422

Gnomad OTH exome

AF:

0.414

GnomAD4 exome

AF:

0.438

AC:

631657

AN:

1441884

Hom.:

141880

Cov.:

AF XY:

0.440

AC XY:

314957

AN XY:

716552

show subpopulations

African (AFR)

AF:

0.537

AC:

17634

AN:

32846

American (AMR)

AF:

0.335

AC:

14229

AN:

42426

Ashkenazi Jewish (ASJ)

AF:

0.407

AC:

10540

AN:

25872

East Asian (EAS)

AF:

0.699

AC:

27459

AN:

39260

South Asian (SAS)

AF:

0.530

AC:

43502

AN:

82006

European-Finnish (FIN)

AF:

0.393

AC:

20872

AN:

53106

Middle Eastern (MID)

AF:

0.452

AC:

2589

AN:

5732

European-Non Finnish (NFE)

AF:

0.425

AC:

467775

AN:

1100982

Other (OTH)

AF:

0.454

AC:

27057

AN:

59654

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

15891

31782

47673

63564

79455

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14450

28900

43350

57800

72250

<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:

0.463

AC:

70339

AN:

151848

Hom.:

16846

Cov.:

AF XY:

0.464

AC XY:

34432

AN XY:

74204

show subpopulations

African (AFR)

AF:

0.542

AC:

22424

AN:

41366

American (AMR)

AF:

0.384

AC:

5863

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.392

AC:

1360

AN:

3466

East Asian (EAS)

AF:

0.749

AC:

3874

AN:

5172

South Asian (SAS)

AF:

0.542

AC:

2607

AN:

4814

European-Finnish (FIN)

AF:

0.386

AC:

4067

AN:

10528

Middle Eastern (MID)

AF:

0.424

AC:

123

AN:

290

European-Non Finnish (NFE)

AF:

0.425

AC:

28869

AN:

67936

Other (OTH)

AF:

0.457

AC:

961

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1896

3792

5689

7585

9481

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

650

1300

1950

2600

3250

<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:

0.425

Hom.:

27479

Bravo

AF:

0.463

Asia WGS

AF:

0.628

AC:

2185

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

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

- -

May 09, 2013

Eurofins Ntd Llc (ga)

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

Asn235Asn in exon 4 of DNAH11: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 47.0% (1718/3656) o f African American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs10950854). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.38

CADD

Benign

3.8

(source)

DANN

Benign

0.65

PhyloP100

0.40

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