rs182389910

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.11233G>A(p.Glu3745Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00282 in 1,613,246 control chromosomes in the GnomAD database, including 52 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. E3745E) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0044 ( 16 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 36 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:7

Conservation

PhyloP100: 1.12

Publications

4 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=0.005862832).

BP6

Variant 7-21861883-G-A is Benign according to our data. Variant chr7-21861883-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 226579.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00438 (666/152140) while in subpopulation AMR AF = 0.0308 (471/15282). AF 95% confidence interval is 0.0285. There are 16 homozygotes in GnomAd4. There are 392 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 16 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.11233G>A	p.Glu3745Lys	missense	Exon 69 of 82	NP_001264044.1	Q96DT5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.11233G>A	p.Glu3745Lys	missense	Exon 69 of 82	ENSP00000475939.1	Q96DT5
DNAH11	ENST00000421290.1	TSL:4	n.416G>A		non_coding_transcript_exon	Exon 4 of 4
DNAH11	ENST00000607413.5	TSL:4	n.496G>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes

AF:

0.00438

AC:

666

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000846

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0309

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00190

Gnomad OTH

AF:

0.00479

GnomAD2 exomes

AF:

0.00569

AC:

1410

AN:

247996

AF XY:

0.00467

show subpopulations

Gnomad AFR exome

AF:

0.000453

Gnomad AMR exome

AF:

0.0323

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00297

Gnomad NFE exome

AF:

0.00160

Gnomad OTH exome

AF:

0.00617

GnomAD4 exome

AF:

0.00266

AC:

3891

AN:

1461106

Hom.:

Cov.:

AF XY:

0.00241

AC XY:

1753

AN XY:

726832

show subpopulations

African (AFR)

AF:

0.000568

AC:

AN:

33442

American (AMR)

AF:

0.0305

AC:

1363

AN:

44652

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39668

South Asian (SAS)

AF:

0.000383

AC:

AN:

86122

European-Finnish (FIN)

AF:

0.00347

AC:

185

AN:

53362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00194

AC:

2153

AN:

1111616

Other (OTH)

AF:

0.00227

AC:

137

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

198

397

595

794

992

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

184

276

368

460

<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:

0.00438

AC:

666

AN:

152140

Hom.:

Cov.:

AF XY:

0.00527

AC XY:

392

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.000843

AC:

AN:

41512

American (AMR)

AF:

0.0308

AC:

471

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4796

European-Finnish (FIN)

AF:

0.00198

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00190

AC:

129

AN:

68010

Other (OTH)

AF:

0.00474

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

126

158

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:

0.00192

Hom.:

Bravo

AF:

0.00576

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000246

AC:

ESP6500EA

AF:

0.00227

AC:

ExAC

AF:

0.00422

AC:

511

EpiCase

AF:

0.00158

EpiControl

AF:

0.00142

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Primary ciliary dyskinesia (3)

not specified (1)

Primary ciliary dyskinesia 7 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.13

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.66

MetaRNN

Benign

0.0059

MetaSVM

Benign

-1.0

PhyloP100

1.1

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.11

Sift

Benign

0.47

Vest4

0.46

MVP

0.38

ClinPred

0.017

GERP RS

-0.00051

Varity_R

0.056

gMVP

0.40

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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