chr7-21854462-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001277115.2(DNAH11):c.11202+7C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0248 in 1,611,074 control chromosomes in the GnomAD database, including 4,470 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.093 ( 1893 hom., cov: 32)

Exomes 𝑓: 0.018 ( 2577 hom. )

Consequence

DNAH11
NM_001277115.2 splice_region, intron

Scores

Splicing: ADA: 0.00009980

Clinical Significance

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

Conservation

PhyloP100: 0.127

Publications

4 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 7-21854462-C-A is Benign according to our data. Variant chr7-21854462-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 163123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.11202+7C>A		splice_region_variant, intron_variant	Intron 68 of 81	ENST00000409508.8	NP_001264044.1	Q96DT5Q96NT7H9NAJ8H9NAJ7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH11	ENST00000409508.8 link	c.11202+7C>A	splice_region_variant, intron_variant	Intron 68 of 81	5	NM_001277115.2	ENSP00000475939.1	Q96DT5
DNAH11	ENST00000421290.1 link	n.385+7C>A	splice_region_variant, intron_variant	Intron 3 of 3	4
DNAH11	ENST00000607413.5 link	n.465+7C>A	splice_region_variant, intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.0934

AC:

14182

AN:

151912

Hom.:

1894

Cov.:

show subpopulations

Gnomad AFR

AF:

0.285

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0348

Gnomad ASJ

AF:

0.00691

Gnomad EAS

AF:

0.220

Gnomad SAS

AF:

0.0118

Gnomad FIN

AF:

0.0303

Gnomad MID

AF:

0.0510

Gnomad NFE

AF:

0.00256

Gnomad OTH

AF:

0.0702

GnomAD2 exomes

AF:

0.0427

AC:

10571

AN:

247478

AF XY:

0.0359

show subpopulations

Gnomad AFR exome

AF:

0.291

Gnomad AMR exome

AF:

0.0238

Gnomad ASJ exome

AF:

0.00847

Gnomad EAS exome

AF:

0.221

Gnomad FIN exome

AF:

0.0303

Gnomad NFE exome

AF:

0.00253

Gnomad OTH exome

AF:

0.0246

GnomAD4 exome

AF:

0.0177

AC:

25775

AN:

1459044

Hom.:

2577

Cov.:

AF XY:

0.0162

AC XY:

11742

AN XY:

725618

show subpopulations

African (AFR)

AF:

0.293

AC:

9739

AN:

33272

American (AMR)

AF:

0.0247

AC:

1098

AN:

44502

Ashkenazi Jewish (ASJ)

AF:

0.00824

AC:

215

AN:

26098

East Asian (EAS)

AF:

0.218

AC:

8599

AN:

39522

South Asian (SAS)

AF:

0.00567

AC:

484

AN:

85422

European-Finnish (FIN)

AF:

0.0279

AC:

1486

AN:

53298

Middle Eastern (MID)

AF:

0.0184

AC:

106

AN:

5762

European-Non Finnish (NFE)

AF:

0.00161

AC:

1794

AN:

1110912

Other (OTH)

AF:

0.0374

AC:

2254

AN:

60256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

893

1786

2679

3572

4465

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

448

896

1344

1792

2240

<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:

0.0933

AC:

14183

AN:

152030

Hom.:

1893

Cov.:

AF XY:

0.0933

AC XY:

6939

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.285

AC:

11776

AN:

41388

American (AMR)

AF:

0.0348

AC:

532

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00691

AC:

AN:

3472

East Asian (EAS)

AF:

0.220

AC:

1139

AN:

5166

South Asian (SAS)

AF:

0.0114

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.0303

AC:

321

AN:

10588

Middle Eastern (MID)

AF:

0.0548

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00254

AC:

173

AN:

67994

Other (OTH)

AF:

0.0695

AC:

147

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

528

1056

1584

2112

2640

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

130

260

390

520

650

<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:

0.0345

Hom.:

291

Bravo

AF:

0.105

Asia WGS

AF:

0.107

AC:

372

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

11202+7C>A in intron 68 of DNAH11: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus se quence. It has been identified in 28.2% (1011/3586) of African American chromoso mes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs .washington.edu/EVS; dbSNP rs73279826). -

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 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

May 24, 2019

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

-0.76

CADD

Benign

0.99

(source)

DANN

Benign

0.59

PhyloP100

0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00010

dbscSNV1_RF

Benign

0.0

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