rs35865357

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001277115.2(DNAH11):c.8990G>A(p.Arg2997Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0165 in 1,613,800 control chromosomes in the GnomAD database, including 277 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2997W) has been classified as Benign.

Frequency

Genomes: 𝑓 0.011 ( 17 hom., cov: 31)

Exomes 𝑓: 0.017 ( 260 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:7

Conservation

PhyloP100: 5.49

Publications

14 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009184986).

BP6

Variant 7-21765477-G-A is Benign according to our data. Variant chr7-21765477-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 163116.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0113 (1720/152198) while in subpopulation NFE AF = 0.0184 (1254/68006). AF 95% confidence interval is 0.0176. There are 17 homozygotes in GnomAd4. There are 820 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 17 AD,AR 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.8990G>A	p.Arg2997Gln	missense	Exon 55 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.8990G>A	p.Arg2997Gln	missense	Exon 55 of 82	ENSP00000475939.1	Q96DT5

Frequencies

GnomAD3 genomes

AF:

0.0113

AC:

1719

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00360

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.00970

Gnomad ASJ

AF:

0.00979

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00685

Gnomad FIN

AF:

0.00650

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0184

Gnomad OTH

AF:

0.00958

GnomAD2 exomes

AF:

0.0112

AC:

2798

AN:

249018

AF XY:

0.0111

show subpopulations

Gnomad AFR exome

AF:

0.00400

Gnomad AMR exome

AF:

0.00684

Gnomad ASJ exome

AF:

0.0110

Gnomad EAS exome

AF:

0.0000557

Gnomad FIN exome

AF:

0.00650

Gnomad NFE exome

AF:

0.0175

Gnomad OTH exome

AF:

0.0144

GnomAD4 exome

AF:

0.0170

AC:

24886

AN:

1461602

Hom.:

260

Cov.:

AF XY:

0.0166

AC XY:

12042

AN XY:

727084

show subpopulations

African (AFR)

AF:

0.00305

AC:

102

AN:

33480

American (AMR)

AF:

0.00715

AC:

320

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0106

AC:

278

AN:

26132

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39698

South Asian (SAS)

AF:

0.00576

AC:

497

AN:

86252

European-Finnish (FIN)

AF:

0.00751

AC:

401

AN:

53388

Middle Eastern (MID)

AF:

0.00485

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0201

AC:

22311

AN:

1111788

Other (OTH)

AF:

0.0157

AC:

946

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

1408

2816

4223

5631

7039

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

842

1684

2526

3368

4210

<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:

0.0113

AC:

1720

AN:

152198

Hom.:

Cov.:

AF XY:

0.0110

AC XY:

820

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.00359

AC:

149

AN:

41524

American (AMR)

AF:

0.00969

AC:

148

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00979

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00707

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00650

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0184

AC:

1254

AN:

68006

Other (OTH)

AF:

0.00948

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

174

260

347

434

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0127

Hom.:

Bravo

AF:

0.0110

TwinsUK

AF:

0.0218

AC:

ALSPAC

AF:

0.0197

AC:

ESP6500AA

AF:

0.00445

AC:

ESP6500EA

AF:

0.0186

AC:

156

ExAC

AF:

0.0109

AC:

1321

Asia WGS

AF:

0.00115

AC:

AN:

3476

EpiCase

AF:

0.0161

EpiControl

AF:

0.0151

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Primary ciliary dyskinesia (2)

Primary ciliary dyskinesia 7 (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.51

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.97

MetaRNN

Benign

0.0092

MetaSVM

Benign

-0.46

PhyloP100

5.5

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-3.7

REVEL

Uncertain

0.30

Sift

Uncertain

0.026

Vest4

0.18

ClinPred

0.046

GERP RS

5.8

Varity_R

0.64

gMVP

0.53

Mutation Taster

=91/9

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over