7-21725834-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.7290C>T(p.Phe2430Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 1,609,990 control chromosomes in the GnomAD database, including 201,438 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14627 hom., cov: 32)

Exomes 𝑓: 0.50 ( 186811 hom. )

Consequence

DNAH11
NM_001277115.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.22

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=-0.32).

BP6

Variant 7-21725834-C-T is Benign according to our data. Variant chr7-21725834-C-T is described in ClinVar as Benign. ClinVar VariationId is 93694.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.22 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277115.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	NM_001277115.2	MANE Select	c.7290C>T	p.Phe2430Phe	synonymous	Exon 45 of 82	NP_001264044.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.7290C>T	p.Phe2430Phe	synonymous	Exon 45 of 82	ENSP00000475939.1

Frequencies

GnomAD3 genomes

AF:

0.425

AC:

64490

AN:

151802

Hom.:

14635

Cov.:

show subpopulations

Gnomad AFR

AF:

0.278

Gnomad AMI

AF:

0.530

Gnomad AMR

AF:

0.431

Gnomad ASJ

AF:

0.407

Gnomad EAS

AF:

0.214

Gnomad SAS

AF:

0.515

Gnomad FIN

AF:

0.484

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.512

Gnomad OTH

AF:

0.429

GnomAD2 exomes

AF:

0.453

AC:

110673

AN:

244124

AF XY:

0.464

show subpopulations

Gnomad AFR exome

AF:

0.268

Gnomad AMR exome

AF:

0.416

Gnomad ASJ exome

AF:

0.404

Gnomad EAS exome

AF:

0.201

Gnomad FIN exome

AF:

0.483

Gnomad NFE exome

AF:

0.510

Gnomad OTH exome

AF:

0.465

GnomAD4 exome

AF:

0.501

AC:

730108

AN:

1458070

Hom.:

186811

Cov.:

AF XY:

0.502

AC XY:

364277

AN XY:

724940

show subpopulations

African (AFR)

AF:

0.265

AC:

8872

AN:

33442

American (AMR)

AF:

0.418

AC:

18498

AN:

44298

Ashkenazi Jewish (ASJ)

AF:

0.402

AC:

10481

AN:

26052

East Asian (EAS)

AF:

0.228

AC:

9051

AN:

39660

South Asian (SAS)

AF:

0.533

AC:

45559

AN:

85426

European-Finnish (FIN)

AF:

0.484

AC:

25756

AN:

53264

Middle Eastern (MID)

AF:

0.423

AC:

2439

AN:

5762

European-Non Finnish (NFE)

AF:

0.523

AC:

580905

AN:

1109892

Other (OTH)

AF:

0.474

AC:

28547

AN:

60274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

16622

33244

49866

66488

83110

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16526

33052

49578

66104

82630

<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:

0.424

AC:

64482

AN:

151920

Hom.:

14627

Cov.:

AF XY:

0.424

AC XY:

31437

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.278

AC:

11505

AN:

41428

American (AMR)

AF:

0.430

AC:

6561

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.407

AC:

1414

AN:

3470

East Asian (EAS)

AF:

0.215

AC:

1112

AN:

5172

South Asian (SAS)

AF:

0.516

AC:

2483

AN:

4810

European-Finnish (FIN)

AF:

0.484

AC:

5103

AN:

10540

Middle Eastern (MID)

AF:

0.391

AC:

115

AN:

294

European-Non Finnish (NFE)

AF:

0.512

AC:

34809

AN:

67932

Other (OTH)

AF:

0.425

AC:

897

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1816

3631

5447

7262

9078

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

606

1212

1818

2424

3030

<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:

0.472

Hom.:

62183

Bravo

AF:

0.410

Asia WGS

AF:

0.318

AC:

1103

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

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

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

Apr 11, 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

Phe2430Phe in exon 45 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 49.2% (4012/8162) of European American chromosomes from a broad population by the NHLBI Exome Seq uencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs12536928).

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Primary ciliary dyskinesia

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: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

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

6.6

(source)

DANN

Benign

0.76

PhyloP100

2.2

Mutation Taster

=89/11

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over