rs72657315

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.4282A>G(p.Thr1428Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00242 in 1,613,654 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0024 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 27 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 4.18

Publications

12 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=0.009599686).

BP6

Variant 7-21619127-A-G is Benign according to our data. Variant chr7-21619127-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 238917.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 = 0.00242 (3534/1461358) while in subpopulation MID AF = 0.0222 (128/5764). AF 95% confidence interval is 0.0191. There are 27 homozygotes in GnomAdExome4. There are 1904 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 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.4282A>G	p.Thr1428Ala	missense	Exon 24 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.4282A>G	p.Thr1428Ala	missense	Exon 24 of 82	ENSP00000475939.1	Q96DT5
	DNAH11	ENST00000465593.1	TSL:2	n.308A>G		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes

AF:

0.00241

AC:

366

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.0432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00176

Gnomad OTH

AF:

0.00716

GnomAD2 exomes

AF:

0.00362

AC:

900

AN:

248940

AF XY:

0.00387

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.00273

Gnomad ASJ exome

AF:

0.0365

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00243

Gnomad OTH exome

AF:

0.00645

GnomAD4 exome

AF:

0.00242

AC:

3534

AN:

1461358

Hom.:

Cov.:

AF XY:

0.00262

AC XY:

1904

AN XY:

726968

show subpopulations

African (AFR)

AF:

0.00123

AC:

AN:

33464

American (AMR)

AF:

0.00266

AC:

119

AN:

44654

Ashkenazi Jewish (ASJ)

AF:

0.0378

AC:

986

AN:

26116

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39692

South Asian (SAS)

AF:

0.00415

AC:

358

AN:

86252

European-Finnish (FIN)

AF:

0.000225

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.0222

AC:

128

AN:

5764

European-Non Finnish (NFE)

AF:

0.00142

AC:

1581

AN:

1111678

Other (OTH)

AF:

0.00509

AC:

307

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

193

386

578

771

964

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

222

296

370

<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:

0.00241

AC:

367

AN:

152296

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

181

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.000385

AC:

AN:

41560

American (AMR)

AF:

0.00170

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0432

AC:

150

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00332

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00176

AC:

120

AN:

68028

Other (OTH)

AF:

0.00709

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

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:

0.00334

Hom.:

Bravo

AF:

0.00265

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000538

AC:

ESP6500EA

AF:

0.00280

AC:

ExAC

AF:

0.00334

AC:

403

EpiCase

AF:

0.00371

EpiControl

AF:

0.00356

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Primary ciliary dyskinesia (1)

Primary ciliary dyskinesia 7 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.74

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.76

MetaRNN

Benign

0.0096

MetaSVM

Benign

-0.87

PhyloP100

4.2

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.9

REVEL

Uncertain

0.30

Sift

Uncertain

0.013

Vest4

0.38

MVP

0.41

ClinPred

0.071

GERP RS

2.9

Varity_R

0.26

gMVP

0.44

Mutation Taster

=97/3

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