5-13811780-C-T

Variant names:

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.7274G>A(p.Arg2425His) variant causes a missense change. The variant allele was found at a frequency of 0.0044 in 1,614,062 control chromosomes in the GnomAD database, including 210 homozygotes. In-silico tool predicts 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. R2425C) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.022 ( 99 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 111 hom. )

Consequence

DNAH5
NM_001369.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 3.98

Publications

7 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, ClinGen
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=0.002856791).

BP6

Variant 5-13811780-C-T is Benign according to our data. Variant chr5-13811780-C-T is described in ClinVar as Benign. ClinVar VariationId is 226606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0698 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.7274G>A	p.Arg2425His	missense	Exon 44 of 79	NP_001360.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.7274G>A	p.Arg2425His	missense	Exon 44 of 79	ENSP00000265104.4
	DNAH5	ENST00000681290.1		c.7229G>A	p.Arg2410His	missense	Exon 44 of 79	ENSP00000505288.1

Frequencies

GnomAD3 genomes

AF:

0.0215

AC:

3276

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0720

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0135

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.0172

GnomAD2 exomes

AF:

0.00642

AC:

1613

AN:

251414

AF XY:

0.00500

show subpopulations

Gnomad AFR exome

AF:

0.0773

Gnomad AMR exome

AF:

0.00656

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000703

Gnomad OTH exome

AF:

0.00407

GnomAD4 exome

AF:

0.00261

AC:

3815

AN:

1461856

Hom.:

111

Cov.:

AF XY:

0.00228

AC XY:

1656

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.0748

AC:

2503

AN:

33476

American (AMR)

AF:

0.00720

AC:

322

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00191

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39686

South Asian (SAS)

AF:

0.000255

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000749

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.0118

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000437

AC:

486

AN:

1112006

Other (OTH)

AF:

0.00594

AC:

359

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

187

374

560

747

934

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

180

270

360

450

<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:

0.0216

AC:

3282

AN:

152206

Hom.:

Cov.:

AF XY:

0.0207

AC XY:

1543

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0719

AC:

2986

AN:

41512

American (AMR)

AF:

0.0135

AC:

206

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.000207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0000944

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000573

AC:

AN:

68022

Other (OTH)

AF:

0.0170

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

155

309

464

618

773

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.00862

Hom.:

Bravo

AF:

0.0252

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0731

AC:

322

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.00752

AC:

913

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.000872

EpiControl

AF:

0.000889

ClinVar

ClinVar submissions as Germline

Significance: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

Benign

0.092

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.092

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.86

MetaRNN

Benign

0.0029

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PhyloP100

4.0

PrimateAI

Benign

0.37

PROVEAN

Benign

-2.0

REVEL

Benign

0.14

Sift

Benign

0.51

Polyphen

0.13

Vest4

0.36

MVP

0.54

MPC

0.12

ClinPred

0.033

GERP RS

5.8

Varity_R

0.15

gMVP

0.58

Mutation Taster

=67/33

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