rs1530496

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.71G>A(p.Gly24Glu) variant causes a missense change. The variant allele was found at a frequency of 0.324 in 1,613,668 control chromosomes in the GnomAD database, including 92,045 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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. G24V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.40 ( 13455 hom., cov: 33)

Exomes 𝑓: 0.32 ( 78590 hom. )

Consequence

DNAH5
NM_001369.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 5.59

Publications

38 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=4.3286577E-6).

BP6

Variant 5-13931231-C-T is Benign according to our data. Variant chr5-13931231-C-T is described in ClinVar as Benign. ClinVar VariationId is 163159.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 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.71G>A	p.Gly24Glu	missense	Exon 2 of 79	NP_001360.1	Q8TE73

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.71G>A	p.Gly24Glu	missense	Exon 2 of 79	ENSP00000265104.4	Q8TE73
DNAH5	ENST00000681290.1		c.26G>A	p.Gly9Glu	missense	Exon 2 of 79	ENSP00000505288.1	A0A7P0Z455
DNAH5	ENST00000508040.1	TSL:2	n.430G>A		non_coding_transcript_exon	Exon 2 of 12

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60659

AN:

151986

Hom.:

13436

Cov.:

show subpopulations

Gnomad AFR

AF:

0.571

Gnomad AMI

AF:

0.274

Gnomad AMR

AF:

0.392

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.698

Gnomad SAS

AF:

0.375

Gnomad FIN

AF:

0.284

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.297

Gnomad OTH

AF:

0.396

GnomAD2 exomes

AF:

0.367

AC:

92279

AN:

251192

AF XY:

0.358

show subpopulations

Gnomad AFR exome

AF:

0.576

Gnomad AMR exome

AF:

0.421

Gnomad ASJ exome

AF:

0.332

Gnomad EAS exome

AF:

0.695

Gnomad FIN exome

AF:

0.271

Gnomad NFE exome

AF:

0.293

Gnomad OTH exome

AF:

0.336

GnomAD4 exome

AF:

0.316

AC:

462539

AN:

1461564

Hom.:

78590

Cov.:

AF XY:

0.316

AC XY:

229815

AN XY:

727088

show subpopulations

African (AFR)

AF:

0.580

AC:

19418

AN:

33462

American (AMR)

AF:

0.423

AC:

18902

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.337

AC:

8796

AN:

26124

East Asian (EAS)

AF:

0.694

AC:

27539

AN:

39686

South Asian (SAS)

AF:

0.357

AC:

30797

AN:

86256

European-Finnish (FIN)

AF:

0.276

AC:

14767

AN:

53410

Middle Eastern (MID)

AF:

0.320

AC:

1845

AN:

5766

European-Non Finnish (NFE)

AF:

0.288

AC:

320310

AN:

1111746

Other (OTH)

AF:

0.334

AC:

20165

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

16340

32680

49019

65359

81699

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10954

21908

32862

43816

54770

<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:

0.399

AC:

60722

AN:

152104

Hom.:

13455

Cov.:

AF XY:

0.398

AC XY:

29605

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.571

AC:

23703

AN:

41506

American (AMR)

AF:

0.393

AC:

5999

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.346

AC:

1200

AN:

3466

East Asian (EAS)

AF:

0.698

AC:

3615

AN:

5176

South Asian (SAS)

AF:

0.374

AC:

1806

AN:

4828

European-Finnish (FIN)

AF:

0.284

AC:

2999

AN:

10564

Middle Eastern (MID)

AF:

0.361

AC:

106

AN:

294

European-Non Finnish (NFE)

AF:

0.297

AC:

20211

AN:

67976

Other (OTH)

AF:

0.395

AC:

833

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1743

3486

5228

6971

8714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

556

1112

1668

2224

2780

<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:

0.337

Hom.:

31549

Bravo

AF:

0.415

TwinsUK

AF:

0.285

AC:

1056

ALSPAC

AF:

0.282

AC:

1085

ESP6500AA

AF:

0.563

AC:

2480

ESP6500EA

AF:

0.302

AC:

2599

ExAC

AF:

0.369

AC:

44816

Asia WGS

AF:

0.508

AC:

1764

AN:

3476

EpiCase

AF:

0.283

EpiControl

AF:

0.287

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 (3)

Primary ciliary dyskinesia 3 (3)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.50

DEOGEN2

Benign

0.019

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.33

MetaRNN

Benign

0.0000043

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-3.0

PhyloP100

5.6

PrimateAI

Benign

0.47

PROVEAN

Benign

4.0

REVEL

Benign

0.15

Sift

Benign

1.0

Polyphen

0.0

Vest4

0.037

MPC

0.12

ClinPred

0.0094

GERP RS

5.6

Varity_R

0.14

gMVP

0.33

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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