rs4429853

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.5115-5T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 1,611,676 control chromosomes in the GnomAD database, including 108,496 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 12597 hom., cov: 32)

Exomes 𝑓: 0.36 ( 95899 hom. )

Consequence

DNAH5
NM_001369.3 splice_region, intron

Scores

Splicing: ADA: 0.00003832

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.128

Publications

9 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 (BayesDel_noAF=-0.92).

BP6

Variant 5-13844998-A-G is Benign according to our data. Variant chr5-13844998-A-G is described in ClinVar as [Benign]. Clinvar id is 163149.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3 link	c.5115-5T>C		splice_region_variant, intron_variant	Intron 31 of 78	ENST00000265104.5	NP_001360.1	Q8TE73

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5 link	c.5115-5T>C		splice_region_variant, intron_variant	Intron 31 of 78	1	NM_001369.3	ENSP00000265104.4		Q8TE73
DNAH5	ENST00000681290.1 link	c.5070-5T>C		splice_region_variant, intron_variant	Intron 31 of 78			ENSP00000505288.1		A0A7P0Z455

Frequencies

GnomAD3 genomes

AF:

0.401

AC:

60853

AN:

151824

Hom.:

12578

Cov.:

show subpopulations

Gnomad AFR

AF:

0.498

Gnomad AMI

AF:

0.416

Gnomad AMR

AF:

0.371

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.607

Gnomad SAS

AF:

0.347

Gnomad FIN

AF:

0.315

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.353

Gnomad OTH

AF:

0.398

GnomAD2 exomes

AF:

0.379

AC:

94931

AN:

250624

AF XY:

0.372

show subpopulations

Gnomad AFR exome

AF:

0.502

Gnomad AMR exome

AF:

0.363

Gnomad ASJ exome

AF:

0.341

Gnomad EAS exome

AF:

0.630

Gnomad FIN exome

AF:

0.320

Gnomad NFE exome

AF:

0.351

Gnomad OTH exome

AF:

0.369

GnomAD4 exome

AF:

0.359

AC:

524248

AN:

1459734

Hom.:

95899

Cov.:

AF XY:

0.358

AC XY:

259714

AN XY:

726308

show subpopulations

African (AFR)

AF:

0.497

AC:

16614

AN:

33418

American (AMR)

AF:

0.369

AC:

16485

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.339

AC:

8849

AN:

26114

East Asian (EAS)

AF:

0.559

AC:

22168

AN:

39684

South Asian (SAS)

AF:

0.339

AC:

29198

AN:

86216

European-Finnish (FIN)

AF:

0.326

AC:

17415

AN:

53370

Middle Eastern (MID)

AF:

0.305

AC:

1757

AN:

5758

European-Non Finnish (NFE)

AF:

0.351

AC:

389436

AN:

1110188

Other (OTH)

AF:

0.370

AC:

22326

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

15687

31374

47061

62748

78435

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.401

AC:

60913

AN:

151942

Hom.:

12597

Cov.:

AF XY:

0.398

AC XY:

29538

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.499

AC:

20652

AN:

41424

American (AMR)

AF:

0.371

AC:

5671

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

1204

AN:

3470

East Asian (EAS)

AF:

0.607

AC:

3128

AN:

5152

South Asian (SAS)

AF:

0.346

AC:

1665

AN:

4806

European-Finnish (FIN)

AF:

0.315

AC:

3327

AN:

10562

Middle Eastern (MID)

AF:

0.296

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.353

AC:

23965

AN:

67944

Other (OTH)

AF:

0.396

AC:

835

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1814

3628

5443

7257

9071

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.368

Hom.:

5558

Bravo

AF:

0.413

Asia WGS

AF:

0.454

AC:

1576

AN:

3478

EpiCase

AF:

0.349

EpiControl

AF:

0.345

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

5115-5T>C in intron 31 of DNAH5: This variant is not expected to have clinical s ignificance because it has been identified in 49.9% (2200/4406) of African Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs4429853). -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Primary ciliary dyskinesia

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 10, 2014

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia 3

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jun 15, 2021

Pars Genome Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.4

(source)

DANN

Benign

0.30

PhyloP100

0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000038

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.050

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.

rs4429853

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over