rs17145720

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.11272T>C(p.Ser3758Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0378 in 1,613,584 control chromosomes in the GnomAD database, including 2,572 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S3758C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.081 ( 1012 hom., cov: 32)

Exomes 𝑓: 0.033 ( 1560 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.223

Publications

15 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 (MetaRNN=0.0031466782).

BP6

Variant 7-21861922-T-C is Benign according to our data. Variant chr7-21861922-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 163125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.11272T>C	p.Ser3758Pro	missense_variant	Exon 69 of 82	ENST00000409508.8	NP_001264044.1	Q96DT5Q96NT7H9NAJ8H9NAJ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH11	ENST00000409508.8 link	c.11272T>C	p.Ser3758Pro	missense_variant	Exon 69 of 82	5	NM_001277115.2	ENSP00000475939.1	Q96DT5
DNAH11	ENST00000421290.1 link	n.455T>C		non_coding_transcript_exon_variant	Exon 4 of 4	4
DNAH11	ENST00000607413.5 link	n.535T>C		non_coding_transcript_exon_variant	Exon 4 of 4	4

Frequencies

GnomAD3 genomes

AF:

0.0809

AC:

12296

AN:

152012

Hom.:

1009

Cov.:

show subpopulations

Gnomad AFR

AF:

0.214

Gnomad AMI

AF:

0.0573

Gnomad AMR

AF:

0.0432

Gnomad ASJ

AF:

0.0521

Gnomad EAS

AF:

0.00348

Gnomad SAS

AF:

0.0360

Gnomad FIN

AF:

0.0209

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0291

Gnomad OTH

AF:

0.0724

GnomAD2 exomes

AF:

0.0393

AC:

9763

AN:

248662

AF XY:

0.0374

show subpopulations

Gnomad AFR exome

AF:

0.220

Gnomad AMR exome

AF:

0.0258

Gnomad ASJ exome

AF:

0.0460

Gnomad EAS exome

AF:

0.00212

Gnomad FIN exome

AF:

0.0217

Gnomad NFE exome

AF:

0.0277

Gnomad OTH exome

AF:

0.0387

GnomAD4 exome

AF:

0.0333

AC:

48707

AN:

1461454

Hom.:

1560

Cov.:

AF XY:

0.0332

AC XY:

24137

AN XY:

726996

show subpopulations

African (AFR)

AF:

0.227

AC:

7600

AN:

33470

American (AMR)

AF:

0.0266

AC:

1189

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.0440

AC:

1149

AN:

26136

East Asian (EAS)

AF:

0.00134

AC:

AN:

39680

South Asian (SAS)

AF:

0.0402

AC:

3467

AN:

86206

European-Finnish (FIN)

AF:

0.0206

AC:

1102

AN:

53388

Middle Eastern (MID)

AF:

0.0548

AC:

316

AN:

5762

European-Non Finnish (NFE)

AF:

0.0281

AC:

31197

AN:

1111750

Other (OTH)

AF:

0.0436

AC:

2634

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

2422

4843

7265

9686

12108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1296

2592

3888

5184

6480

<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:

0.0810

AC:

12315

AN:

152130

Hom.:

1012

Cov.:

AF XY:

0.0799

AC XY:

5945

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.214

AC:

8866

AN:

41460

American (AMR)

AF:

0.0430

AC:

658

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0521

AC:

181

AN:

3472

East Asian (EAS)

AF:

0.00349

AC:

AN:

5162

South Asian (SAS)

AF:

0.0357

AC:

172

AN:

4824

European-Finnish (FIN)

AF:

0.0209

AC:

221

AN:

10598

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0291

AC:

1978

AN:

68012

Other (OTH)

AF:

0.0726

AC:

153

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

522

1044

1566

2088

2610

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:

0.0406

Hom.:

1084

Bravo

AF:

0.0895

TwinsUK

AF:

0.0229

AC:

ALSPAC

AF:

0.0293

AC:

113

ESP6500AA

AF:

0.202

AC:

833

ESP6500EA

AF:

0.0281

AC:

237

ExAC

AF:

0.0418

AC:

5054

Asia WGS

AF:

0.0530

AC:

182

AN:

3478

EpiCase

AF:

0.0289

EpiControl

AF:

0.0318

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

Significance:Benign

Review Status:no assertion criteria provided

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

Ser3758Pro in exon 69 of DNAH11: This variant is not expected to have clinical s ignificance because it has been identified in 20.2% (833/4116) of African Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs17145720). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 17, 2018

GeneDx

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.18

.;.;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.57

T;T;T

MetaRNN

Benign

0.0031

T;T;T

MetaSVM

Benign

-1.0

PhyloP100

-0.22

PrimateAI

Benign

0.29

PROVEAN

Benign

-2.3

.;N;.

REVEL

Benign

0.23

Sift

Benign

0.27

.;T;.

Vest4

0.16

ClinPred

0.024

GERP RS

5.7

Varity_R

0.31

gMVP

0.65

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