7-21735769-T-C

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.7570T>C(p.Leu2524Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0606 in 1,613,770 control chromosomes in the GnomAD database, including 6,619 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1799 hom., cov: 33)

Exomes 𝑓: 0.055 ( 4820 hom. )

Consequence

DNAH11
NM_001277115.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.995

Publications

12 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=-0.73).

BP6

Variant 7-21735769-T-C is Benign according to our data. Variant chr7-21735769-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 163109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.995 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.7570T>C	p.Leu2524Leu	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.7570T>C	p.Leu2524Leu	synonymous_variant	Exon 46 of 82	5	NM_001277115.2	ENSP00000475939.1
DNAH11	ENST00000605912.1 link	c.130T>C	p.Leu44Leu	synonymous_variant	Exon 1 of 4	3		ENSP00000476068.1

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17668

AN:

152052

Hom.:

1791

Cov.:

show subpopulations

Gnomad AFR

AF:

0.247

Gnomad AMI

AF:

0.0362

Gnomad AMR

AF:

0.181

Gnomad ASJ

AF:

0.0591

Gnomad EAS

AF:

0.204

Gnomad SAS

AF:

0.0665

Gnomad FIN

AF:

0.0402

Gnomad MID

AF:

0.0987

Gnomad NFE

AF:

0.0353

Gnomad OTH

AF:

0.108

GnomAD2 exomes

AF:

0.0973

AC:

24236

AN:

249190

AF XY:

0.0869

show subpopulations

Gnomad AFR exome

AF:

0.250

Gnomad AMR exome

AF:

0.251

Gnomad ASJ exome

AF:

0.0651

Gnomad EAS exome

AF:

0.208

Gnomad FIN exome

AF:

0.0403

Gnomad NFE exome

AF:

0.0355

Gnomad OTH exome

AF:

0.0802

GnomAD4 exome

AF:

0.0548

AC:

80113

AN:

1461600

Hom.:

4820

Cov.:

AF XY:

0.0536

AC XY:

39000

AN XY:

727082

show subpopulations

African (AFR)

AF:

0.249

AC:

8345

AN:

33470

American (AMR)

AF:

0.242

AC:

10802

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0676

AC:

1767

AN:

26132

East Asian (EAS)

AF:

0.232

AC:

9220

AN:

39694

South Asian (SAS)

AF:

0.0576

AC:

4971

AN:

86254

European-Finnish (FIN)

AF:

0.0390

AC:

2081

AN:

53398

Middle Eastern (MID)

AF:

0.0600

AC:

346

AN:

5768

European-Non Finnish (NFE)

AF:

0.0345

AC:

38405

AN:

1111800

Other (OTH)

AF:

0.0692

AC:

4176

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

3742

7484

11227

14969

18711

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1824

3648

5472

7296

9120

<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:

0.116

AC:

17707

AN:

152170

Hom.:

1799

Cov.:

AF XY:

0.117

AC XY:

8706

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.247

AC:

10244

AN:

41486

American (AMR)

AF:

0.182

AC:

2784

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0591

AC:

205

AN:

3470

East Asian (EAS)

AF:

0.204

AC:

1054

AN:

5176

South Asian (SAS)

AF:

0.0651

AC:

314

AN:

4820

European-Finnish (FIN)

AF:

0.0402

AC:

426

AN:

10596

Middle Eastern (MID)

AF:

0.0856

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0352

AC:

2397

AN:

68020

Other (OTH)

AF:

0.106

AC:

225

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

736

1472

2207

2943

3679

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

174

348

522

696

870

<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:

0.0656

Hom.:

3156

Bravo

AF:

0.136

EpiCase

AF:

0.0374

EpiControl

AF:

0.0407

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

Leu2524Leu 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 22.3% (860/3850) of African American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2072220). -

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:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 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

-0.73

CADD

Benign

1.7

(source)

DANN

Benign

0.26

PhyloP100

0.99

PromoterAI

0.0090

Neutral

(source)

Mutation Taster

=99/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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