rs77448980

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.13502A>G(p.Lys4501Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.076 in 1,613,064 control chromosomes in the GnomAD database, including 5,191 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.062 ( 328 hom., cov: 33)

Exomes 𝑓: 0.077 ( 4863 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.797

Publications

9 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 links:

CDCA7L (HGNC:30777): (cell division cycle associated 7 like) Acts upstream of or within positive regulation of cell population proliferation. Located in cytosol; fibrillar center; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CDCA7L 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=0.0018184781).

BP6

Variant 7-21901205-A-G is Benign according to our data. Variant chr7-21901205-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 163130.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
DNAH11	NM_001277115.2 link	c.13502A>G	p.Lys4501Arg	missense_variant	Exon 82 of 82	ENST00000409508.8	NP_001264044.1
CDCA7L	NM_018719.5 link	c.*1117T>C		3_prime_UTR_variant	Exon 10 of 10	ENST00000406877.8	NP_061189.2
CDCA7L	NM_001127370.3 link	c.*1117T>C		3_prime_UTR_variant	Exon 11 of 11		NP_001120842.1
CDCA7L	NM_001127371.3 link	c.*1117T>C		3_prime_UTR_variant	Exon 9 of 9		NP_001120843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8 link	c.13502A>G	p.Lys4501Arg	missense_variant	Exon 82 of 82	5	NM_001277115.2	ENSP00000475939.1
CDCA7L	ENST00000406877.8 link	c.*1117T>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_018719.5	ENSP00000383986.3

Frequencies

GnomAD3 genomes

AF:

0.0619

AC:

9401

AN:

151988

Hom.:

325

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0385

Gnomad AMI

AF:

0.185

Gnomad AMR

AF:

0.0389

Gnomad ASJ

AF:

0.0525

Gnomad EAS

AF:

0.0273

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.0592

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0800

Gnomad OTH

AF:

0.0582

GnomAD2 exomes

AF:

0.0668

AC:

16502

AN:

246936

AF XY:

0.0707

show subpopulations

Gnomad AFR exome

AF:

0.0388

Gnomad AMR exome

AF:

0.0269

Gnomad ASJ exome

AF:

0.0572

Gnomad EAS exome

AF:

0.0300

Gnomad FIN exome

AF:

0.0602

Gnomad NFE exome

AF:

0.0802

Gnomad OTH exome

AF:

0.0637

GnomAD4 exome

AF:

0.0775

AC:

113166

AN:

1460958

Hom.:

4863

Cov.:

AF XY:

0.0784

AC XY:

56943

AN XY:

726744

show subpopulations

African (AFR)

AF:

0.0393

AC:

1316

AN:

33470

American (AMR)

AF:

0.0280

AC:

1253

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.0550

AC:

1436

AN:

26124

East Asian (EAS)

AF:

0.0159

AC:

631

AN:

39700

South Asian (SAS)

AF:

0.106

AC:

9164

AN:

86214

European-Finnish (FIN)

AF:

0.0630

AC:

3362

AN:

53402

Middle Eastern (MID)

AF:

0.0676

AC:

390

AN:

5768

European-Non Finnish (NFE)

AF:

0.0821

AC:

91211

AN:

1111272

Other (OTH)

AF:

0.0730

AC:

4403

AN:

60328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

6013

12026

18038

24051

30064

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3334

6668

10002

13336

16670

<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:

0.0619

AC:

9416

AN:

152106

Hom.:

328

Cov.:

AF XY:

0.0604

AC XY:

4495

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.0387

AC:

1608

AN:

41532

American (AMR)

AF:

0.0387

AC:

591

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.0525

AC:

182

AN:

3466

East Asian (EAS)

AF:

0.0274

AC:

142

AN:

5180

South Asian (SAS)

AF:

0.108

AC:

522

AN:

4812

European-Finnish (FIN)

AF:

0.0592

AC:

628

AN:

10610

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0799

AC:

5431

AN:

67940

Other (OTH)

AF:

0.0595

AC:

125

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

444

888

1332

1776

2220

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<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:

0.0717

Hom.:

869

Bravo

AF:

0.0582

TwinsUK

AF:

0.0831

AC:

308

ALSPAC

AF:

0.0755

AC:

291

ESP6500AA

AF:

0.0423

AC:

163

ESP6500EA

AF:

0.0822

AC:

682

ExAC

AF:

0.0703

AC:

8504

Asia WGS

AF:

0.0870

AC:

300

AN:

3478

EpiCase

AF:

0.0787

EpiControl

AF:

0.0756

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

PreventionGenetics, part of Exact Sciences

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

Lys4501Arg in exon 82 of DNAH11: This variant is not expected to have clinical s ignificance because it has been identified in 8.2% (682/8292) of European Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs77448980). -

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

- -

Feb 18, 2019

GeneDx

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

0.080

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.71

CADD

Benign

7.5

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.059

.;.;T

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.67

T;T;T

MetaRNN

Benign

0.0018

T;T;T

MetaSVM

Benign

-0.95

PhyloP100

0.80

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.6

.;N;.

REVEL

Benign

0.043

Sift

Benign

0.37

.;T;.

Vest4

0.038

ClinPred

0.0029

GERP RS

3.6

Varity_R

0.032

gMVP

0.17

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