chr7-21738811-T-C

Variant names:

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.7756T>C(p.Tyr2586His) variant causes a missense change. The variant allele was found at a frequency of 0.0508 in 1,604,626 control chromosomes in the GnomAD database, including 2,372 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. Y2586Y) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.034 ( 132 hom., cov: 32)

Exomes 𝑓: 0.053 ( 2240 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 6.28

Publications

11 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=0.0071105957).

BP6

Variant 7-21738811-T-C is Benign according to our data. Variant chr7-21738811-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 163111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0544 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.7756T>C	p.Tyr2586His	missense	Exon 47 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.7756T>C	p.Tyr2586His	missense	Exon 47 of 82	ENSP00000475939.1	Q96DT5
	DNAH11	ENST00000605912.1	TSL:3	c.316T>C	p.Tyr106His	missense	Exon 2 of 4	ENSP00000476068.1	U3KQN2

Frequencies

GnomAD3 genomes

AF:

0.0344

AC:

5235

AN:

152130

Hom.:

132

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00987

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.0200

Gnomad ASJ

AF:

0.0225

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0230

Gnomad FIN

AF:

0.0418

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0559

Gnomad OTH

AF:

0.0287

GnomAD2 exomes

AF:

0.0374

AC:

8811

AN:

235612

AF XY:

0.0377

show subpopulations

Gnomad AFR exome

AF:

0.00878

Gnomad AMR exome

AF:

0.0223

Gnomad ASJ exome

AF:

0.0219

Gnomad EAS exome

AF:

0.0000572

Gnomad FIN exome

AF:

0.0416

Gnomad NFE exome

AF:

0.0559

Gnomad OTH exome

AF:

0.0341

GnomAD4 exome

AF:

0.0526

AC:

76332

AN:

1452378

Hom.:

2240

Cov.:

AF XY:

0.0516

AC XY:

37214

AN XY:

721364

show subpopulations

African (AFR)

AF:

0.00762

AC:

254

AN:

33318

American (AMR)

AF:

0.0216

AC:

950

AN:

43978

Ashkenazi Jewish (ASJ)

AF:

0.0248

AC:

643

AN:

25898

East Asian (EAS)

AF:

0.0000759

AC:

AN:

39508

South Asian (SAS)

AF:

0.0283

AC:

2380

AN:

84010

European-Finnish (FIN)

AF:

0.0420

AC:

2222

AN:

52864

Middle Eastern (MID)

AF:

0.00956

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0606

AC:

67048

AN:

1106982

Other (OTH)

AF:

0.0462

AC:

2777

AN:

60066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

3549

7099

10648

14198

17747

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2512

5024

7536

10048

12560

<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:

0.0344

AC:

5231

AN:

152248

Hom.:

132

Cov.:

AF XY:

0.0327

AC XY:

2433

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.00984

AC:

409

AN:

41554

American (AMR)

AF:

0.0199

AC:

304

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0225

AC:

AN:

3466

East Asian (EAS)

AF:

0.00116

AC:

AN:

5178

South Asian (SAS)

AF:

0.0226

AC:

109

AN:

4818

European-Finnish (FIN)

AF:

0.0418

AC:

443

AN:

10604

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0559

AC:

3803

AN:

68010

Other (OTH)

AF:

0.0284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

259

518

776

1035

1294

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<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:

0.0490

Hom.:

710

Bravo

AF:

0.0324

TwinsUK

AF:

0.0623

AC:

231

ALSPAC

AF:

0.0649

AC:

250

ESP6500AA

AF:

0.0152

AC:

ESP6500EA

AF:

0.0550

AC:

471

ExAC

AF:

0.0375

AC:

4542

Asia WGS

AF:

0.00751

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Primary ciliary dyskinesia (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.54

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.99

MetaRNN

Benign

0.0071

MetaSVM

Benign

-0.77

PhyloP100

6.3

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-4.7

REVEL

Uncertain

0.43

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.21

ClinPred

0.053

GERP RS

5.4

Varity_R

0.76

gMVP

0.59

Mutation Taster

=97/3

polymorphism (auto)

(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