rs17263496

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_001369.3(DNAH5):c.11372C>T(p.Thr3791Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,613,910 control chromosomes in the GnomAD database, including 13,130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1030 hom., cov: 32)

Exomes 𝑓: 0.12 ( 12100 hom. )

Consequence

DNAH5
NM_001369.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 8.04

Publications

25 publications found

Variant links:

Genes affected

DNAH5 (HGNC:2950): (dynein axonemal heavy chain 5) This gene encodes a dynein protein, which is part of a microtubule-associated motor protein complex consisting of heavy, light, and intermediate chains. This protein is an axonemal heavy chain dynein. It functions as a force-generating protein with ATPase activity, whereby the release of ADP is thought to produce the force-producing power stroke. Mutations in this gene cause primary ciliary dyskinesia type 3, as well as Kartagener syndrome, which are both diseases due to ciliary defects. [provided by RefSeq, Oct 2009]

DNAH5 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 3
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAH5 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=0.001767695).

BP6

Variant 5-13737335-G-A is Benign according to our data. Variant chr5-13737335-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 178744.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369.3. 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
	DNAH5	NM_001369.3	MANE Select	c.11372C>T	p.Thr3791Ile	missense	Exon 66 of 79	NP_001360.1	Q8TE73

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.11372C>T	p.Thr3791Ile	missense	Exon 66 of 79	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.11327C>T	p.Thr3776Ile	missense	Exon 66 of 79	ENSP00000505288.1	A0A7P0Z455

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15522

AN:

152022

Hom.:

1030

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0336

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.0923

Gnomad ASJ

AF:

0.150

Gnomad EAS

AF:

0.0493

Gnomad SAS

AF:

0.0423

Gnomad FIN

AF:

0.215

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.133

Gnomad OTH

AF:

0.109

GnomAD2 exomes

AF:

0.104

AC:

26255

AN:

251364

AF XY:

0.103

show subpopulations

Gnomad AFR exome

AF:

0.0299

Gnomad AMR exome

AF:

0.0619

Gnomad ASJ exome

AF:

0.148

Gnomad EAS exome

AF:

0.0403

Gnomad FIN exome

AF:

0.204

Gnomad NFE exome

AF:

0.133

Gnomad OTH exome

AF:

0.116

GnomAD4 exome

AF:

0.123

AC:

179440

AN:

1461770

Hom.:

12100

Cov.:

AF XY:

0.121

AC XY:

87866

AN XY:

727200

show subpopulations

African (AFR)

AF:

0.0285

AC:

955

AN:

33478

American (AMR)

AF:

0.0658

AC:

2943

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.149

AC:

3886

AN:

26132

East Asian (EAS)

AF:

0.0503

AC:

1995

AN:

39694

South Asian (SAS)

AF:

0.0377

AC:

3255

AN:

86258

European-Finnish (FIN)

AF:

0.198

AC:

10572

AN:

53418

Middle Eastern (MID)

AF:

0.0811

AC:

468

AN:

5768

European-Non Finnish (NFE)

AF:

0.134

AC:

148687

AN:

1111914

Other (OTH)

AF:

0.111

AC:

6679

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

9357

18714

28071

37428

46785

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5200

10400

15600

20800

26000

<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:

0.102

AC:

15519

AN:

152140

Hom.:

1030

Cov.:

AF XY:

0.104

AC XY:

7719

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.0336

AC:

1394

AN:

41530

American (AMR)

AF:

0.0921

AC:

1406

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

520

AN:

3470

East Asian (EAS)

AF:

0.0490

AC:

254

AN:

5182

South Asian (SAS)

AF:

0.0425

AC:

205

AN:

4824

European-Finnish (FIN)

AF:

0.215

AC:

2273

AN:

10558

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.133

AC:

9070

AN:

67992

Other (OTH)

AF:

0.109

AC:

230

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

685

1369

2054

2738

3423

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

166

332

498

664

830

<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:

0.120

Hom.:

4924

Bravo

AF:

0.0910

TwinsUK

AF:

0.137

AC:

509

ALSPAC

AF:

0.139

AC:

536

ESP6500AA

AF:

0.0306

AC:

135

ESP6500EA

AF:

0.127

AC:

1092

ExAC

AF:

0.101

AC:

12283

Asia WGS

AF:

0.0500

AC:

173

AN:

3478

EpiCase

AF:

0.126

EpiControl

AF:

0.125

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Primary ciliary dyskinesia (3)

not provided (2)

not specified (2)

Primary ciliary dyskinesia 3 (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.58

Eigen

Pathogenic

0.94

Eigen_PC

Pathogenic

0.89

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

MetaRNN

Benign

0.0018

MetaSVM

Benign

-0.93

MutationAssessor

Pathogenic

3.4

PhyloP100

8.0

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-5.3

REVEL

Uncertain

0.40

Sift

Uncertain

0.0010

Polyphen

0.99

Vest4

0.35

MPC

0.41

ClinPred

0.053

GERP RS

5.4

Varity_R

0.89

gMVP

0.58

Mutation Taster

=85/15

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