rs34879202

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.10739G>A(p.Arg3580His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 1,613,800 control chromosomes in the GnomAD database, including 184 homozygotes. In-silico tool predicts 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. R3580C) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0093 ( 10 hom., cov: 32)

Exomes 𝑓: 0.014 ( 174 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.52

Publications

7 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: Labcorp Genetics (formerly Invitae), ClinGen, Laboratory for Molecular Medicine
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=0.012826085).

BP6

Variant 7-21842591-G-A is Benign according to our data. Variant chr7-21842591-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 178733.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00926 (1409/152224) while in subpopulation NFE AF = 0.0152 (1036/68012). AF 95% confidence interval is 0.0145. There are 10 homozygotes in GnomAd4. There are 670 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 10 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277115.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	NM_001277115.2	MANE Select	c.10739G>A	p.Arg3580His	missense	Exon 66 of 82	NP_001264044.1	Q96DT5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.10739G>A	p.Arg3580His	missense	Exon 66 of 82	ENSP00000475939.1	Q96DT5

Frequencies

GnomAD3 genomes

AF:

0.00926

AC:

1408

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00316

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.00812

Gnomad ASJ

AF:

0.00923

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00559

Gnomad FIN

AF:

0.00311

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0152

Gnomad OTH

AF:

0.00621

GnomAD2 exomes

AF:

0.00873

AC:

2175

AN:

249044

AF XY:

0.00858

show subpopulations

Gnomad AFR exome

AF:

0.00368

Gnomad AMR exome

AF:

0.00443

Gnomad ASJ exome

AF:

0.0107

Gnomad EAS exome

AF:

0.0000556

Gnomad FIN exome

AF:

0.00339

Gnomad NFE exome

AF:

0.0141

Gnomad OTH exome

AF:

0.00993

GnomAD4 exome

AF:

0.0143

AC:

20876

AN:

1461576

Hom.:

174

Cov.:

AF XY:

0.0139

AC XY:

10114

AN XY:

727070

show subpopulations

African (AFR)

AF:

0.00284

AC:

AN:

33476

American (AMR)

AF:

0.00458

AC:

205

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0106

AC:

278

AN:

26130

East Asian (EAS)

AF:

0.000101

AC:

AN:

39688

South Asian (SAS)

AF:

0.00413

AC:

356

AN:

86252

European-Finnish (FIN)

AF:

0.00365

AC:

195

AN:

53382

Middle Eastern (MID)

AF:

0.00451

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0170

AC:

18920

AN:

1111790

Other (OTH)

AF:

0.0132

AC:

797

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

1007

2014

3020

4027

5034

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

712

1424

2136

2848

3560

<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:

0.00926

AC:

1409

AN:

152224

Hom.:

Cov.:

AF XY:

0.00900

AC XY:

670

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.00315

AC:

131

AN:

41536

American (AMR)

AF:

0.00811

AC:

124

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00923

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00581

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00311

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0152

AC:

1036

AN:

68012

Other (OTH)

AF:

0.00615

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

146

218

291

364

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.0115

Hom.:

Bravo

AF:

0.00881

TwinsUK

AF:

0.0194

AC:

ALSPAC

AF:

0.0148

AC:

ESP6500AA

AF:

0.00451

AC:

ESP6500EA

AF:

0.0148

AC:

122

ExAC

AF:

0.00848

AC:

1025

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0145

EpiControl

AF:

0.0120

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (2)

Primary ciliary dyskinesia 7 (2)

Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.96

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.66

PhyloP100

1.5

PrimateAI

Benign

0.27

PROVEAN

Pathogenic

-4.7

REVEL

Uncertain

0.30

Sift

Uncertain

0.023

Vest4

0.79

MVP

0.36

ClinPred

0.020

GERP RS

5.4

Varity_R

0.32

gMVP

0.58

Mutation Taster

=72/28

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over