rs10224537

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_StrongBA1

The NM_001277115.2(DNAH11):c.3112A>G(p.Thr1038Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 1,613,570 control chromosomes in the GnomAD database, including 543,034 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1038V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.80 ( 48351 hom., cov: 30)

Exomes 𝑓: 0.82 ( 494683 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.361

Publications

34 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=7.558386E-7).

BP6

Variant 7-21600787-A-G is Benign according to our data. Variant chr7-21600787-A-G is described in ClinVar as Benign. ClinVar VariationId is 163100.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

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.3112A>G	p.Thr1038Ala	missense	Exon 16 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.3112A>G	p.Thr1038Ala	missense	Exon 16 of 82	ENSP00000475939.1	Q96DT5

Frequencies

GnomAD3 genomes

AF:

0.796

AC:

120916

AN:

151858

Hom.:

48310

Cov.:

show subpopulations

Gnomad AFR

AF:

0.752

Gnomad AMI

AF:

0.857

Gnomad AMR

AF:

0.723

Gnomad ASJ

AF:

0.740

Gnomad EAS

AF:

0.820

Gnomad SAS

AF:

0.717

Gnomad FIN

AF:

0.821

Gnomad MID

AF:

0.709

Gnomad NFE

AF:

0.842

Gnomad OTH

AF:

0.796

GnomAD2 exomes

AF:

0.782

AC:

194303

AN:

248324

AF XY:

0.784

show subpopulations

Gnomad AFR exome

AF:

0.745

Gnomad AMR exome

AF:

0.655

Gnomad ASJ exome

AF:

0.735

Gnomad EAS exome

AF:

0.811

Gnomad FIN exome

AF:

0.827

Gnomad NFE exome

AF:

0.839

Gnomad OTH exome

AF:

0.792

GnomAD4 exome

AF:

0.821

AC:

1200035

AN:

1461594

Hom.:

494683

Cov.:

AF XY:

0.818

AC XY:

594577

AN XY:

727086

show subpopulations

African (AFR)

AF:

0.738

AC:

24693

AN:

33474

American (AMR)

AF:

0.665

AC:

29727

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.735

AC:

19213

AN:

26134

East Asian (EAS)

AF:

0.790

AC:

31351

AN:

39694

South Asian (SAS)

AF:

0.707

AC:

60972

AN:

86248

European-Finnish (FIN)

AF:

0.833

AC:

44477

AN:

53400

Middle Eastern (MID)

AF:

0.713

AC:

4112

AN:

5764

European-Non Finnish (NFE)

AF:

0.842

AC:

936294

AN:

1111796

Other (OTH)

AF:

0.815

AC:

49196

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

13233

26465

39698

52930

66163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21036

42072

63108

84144

105180

<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:

0.796

AC:

121007

AN:

151976

Hom.:

48351

Cov.:

AF XY:

0.790

AC XY:

58717

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.752

AC:

31148

AN:

41414

American (AMR)

AF:

0.722

AC:

11016

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.740

AC:

2571

AN:

3472

East Asian (EAS)

AF:

0.820

AC:

4221

AN:

5148

South Asian (SAS)

AF:

0.716

AC:

3437

AN:

4798

European-Finnish (FIN)

AF:

0.821

AC:

8685

AN:

10578

Middle Eastern (MID)

AF:

0.714

AC:

210

AN:

294

European-Non Finnish (NFE)

AF:

0.842

AC:

57251

AN:

67992

Other (OTH)

AF:

0.799

AC:

1686

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1233

2466

3700

4933

6166

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

872

1744

2616

3488

4360

<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:

0.822

Hom.:

255063

Bravo

AF:

0.788

TwinsUK

AF:

0.847

AC:

3142

ALSPAC

AF:

0.849

AC:

3272

ESP6500AA

AF:

0.768

AC:

3046

ESP6500EA

AF:

0.838

AC:

6987

ExAC

AF:

0.788

AC:

95266

Asia WGS

AF:

0.810

AC:

2820

AN:

3478

EpiCase

AF:

0.835

EpiControl

AF:

0.830

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

Primary ciliary dyskinesia (2)

not provided (1)

Primary ciliary dyskinesia 7 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

8.7

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.014

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.047

MetaRNN

Benign

7.6e-7

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.9

PhyloP100

0.36

PrimateAI

Benign

0.29

PROVEAN

Benign

1.2

REVEL

Benign

0.019

Sift

Benign

0.44

Polyphen

0.0

Vest4

0.018

ClinPred

0.0011

GERP RS

3.6

Varity_R

0.044

gMVP

0.17

Mutation Taster

=97/3

polymorphism (auto)

(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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over