rs143362381

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_StrongBS1BS2

The NM_001277115.2(DNAH11):c.13495G>A(p.Glu4499Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00367 in 1,613,662 control chromosomes in the GnomAD database, including 50 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E4499D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0040 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0036 ( 43 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.04

Publications

10 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=0.002060622).

BP6

Variant 7-21901198-G-A is Benign according to our data. Variant chr7-21901198-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 226581.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00363 (5312/1461600) while in subpopulation MID AF = 0.00433 (25/5768). AF 95% confidence interval is 0.00308. There are 43 homozygotes in GnomAdExome4. There are 2634 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 7 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
DNAH11	NM_001277115.2 link	c.13495G>A	p.Glu4499Lys	missense_variant	Exon 82 of 82	ENST00000409508.8	NP_001264044.1
CDCA7L	NM_018719.5 link	c.*1124C>T		3_prime_UTR_variant	Exon 10 of 10	ENST00000406877.8	NP_061189.2
CDCA7L	NM_001127370.3 link	c.*1124C>T		3_prime_UTR_variant	Exon 11 of 11		NP_001120842.1
CDCA7L	NM_001127371.3 link	c.*1124C>T		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.13495G>A	p.Glu4499Lys	missense_variant	Exon 82 of 82	5	NM_001277115.2	ENSP00000475939.1
CDCA7L	ENST00000406877.8 link	c.*1124C>T		3_prime_UTR_variant	Exon 10 of 10	1	NM_018719.5	ENSP00000383986.3

Frequencies

GnomAD3 genomes

AF:

0.00398

AC:

604

AN:

151946

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.00314

Gnomad FIN

AF:

0.0290

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00297

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.00458

AC:

1131

AN:

247058

AF XY:

0.00450

show subpopulations

Gnomad AFR exome

AF:

0.000517

Gnomad AMR exome

AF:

0.00122

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00217

Gnomad FIN exome

AF:

0.0269

Gnomad NFE exome

AF:

0.00330

Gnomad OTH exome

AF:

0.00298

GnomAD4 exome

AF:

0.00363

AC:

5312

AN:

1461600

Hom.:

Cov.:

AF XY:

0.00362

AC XY:

2634

AN XY:

727068

show subpopulations

African (AFR)

AF:

0.000777

AC:

AN:

33476

American (AMR)

AF:

0.00119

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000383

AC:

AN:

26134

East Asian (EAS)

AF:

0.00166

AC:

AN:

39698

South Asian (SAS)

AF:

0.00249

AC:

215

AN:

86214

European-Finnish (FIN)

AF:

0.0232

AC:

1237

AN:

53402

Middle Eastern (MID)

AF:

0.00433

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00316

AC:

3518

AN:

1111816

Other (OTH)

AF:

0.00268

AC:

162

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

308

617

925

1234

1542

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.00397

AC:

604

AN:

152062

Hom.:

Cov.:

AF XY:

0.00518

AC XY:

385

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.000674

AC:

AN:

41522

American (AMR)

AF:

0.00242

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00194

AC:

AN:

5164

South Asian (SAS)

AF:

0.00314

AC:

AN:

4780

European-Finnish (FIN)

AF:

0.0290

AC:

307

AN:

10588

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00297

AC:

202

AN:

67942

Other (OTH)

AF:

0.00190

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

122

152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00258

Hom.:

Bravo

AF:

0.00193

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.00253

AC:

ExAC

AF:

0.00400

AC:

484

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00207

EpiControl

AF:

0.00344

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 09, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Glu4499Lys in exon 82 of DNAH11: This variant has been identified in 2.48% (1 64/6614) of Finnish chromosomes by the Exome Aggregation Consortium (ExAC, http: //exac.broadinstitute.org; dbSNP rs143362381). -

Primary ciliary dyskinesia

Benign:2

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 30, 2015

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:2

May 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

DNAH11: BP4 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Primary ciliary dyskinesia 7

Benign:1

Oct 26, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.67

CADD

Benign

6.1

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.013

.;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.52

T;T;T

MetaRNN

Benign

0.0021

T;T;T

MetaSVM

Benign

-0.90

PhyloP100

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

3.1

.;N;.

REVEL

Benign

0.032

Sift

Benign

1.0

.;T;.

Vest4

0.16

MVP

0.085

ClinPred

0.0019

GERP RS

0.46

Varity_R

0.025

gMVP

0.16

Mutation Taster

=100/0

polymorphism

(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

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