5-13900236-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001369.3(DNAH5):c.2229T>C(p.Asp743Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 1,613,110 control chromosomes in the GnomAD database, including 186,553 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 22023 hom., cov: 32)

Exomes 𝑓: 0.47 ( 164530 hom. )

Consequence

DNAH5
NM_001369.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0730

Publications

23 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:

ENSG00000251423 (HGNC:40187):

ENSG00000251423 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 5-13900236-A-G is Benign according to our data. Variant chr5-13900236-A-G is described in ClinVar as [Benign]. Clinvar id is 178755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.073 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3 link	c.2229T>C	p.Asp743Asp	synonymous_variant	Exon 15 of 79	ENST00000265104.5	NP_001360.1	Q8TE73

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH5	ENST00000265104.5 link	c.2229T>C	p.Asp743Asp	synonymous_variant	Exon 15 of 79	1	NM_001369.3	ENSP00000265104.4	Q8TE73
DNAH5	ENST00000681290.1 link	c.2184T>C	p.Asp728Asp	synonymous_variant	Exon 15 of 79			ENSP00000505288.1	A0A7P0Z455
ENSG00000251423	ENST00000503244.2 link	n.3112A>G		non_coding_transcript_exon_variant	Exon 3 of 3	4
ENSG00000251423	ENST00000637153.1 link	n.3072A>G		non_coding_transcript_exon_variant	Exon 3 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.526

AC:

80009

AN:

151980

Hom.:

22013

Cov.:

show subpopulations

Gnomad AFR

AF:

0.661

Gnomad AMI

AF:

0.414

Gnomad AMR

AF:

0.479

Gnomad ASJ

AF:

0.478

Gnomad EAS

AF:

0.876

Gnomad SAS

AF:

0.453

Gnomad FIN

AF:

0.424

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.454

Gnomad OTH

AF:

0.503

GnomAD2 exomes

AF:

0.500

AC:

125510

AN:

251038

AF XY:

0.492

show subpopulations

Gnomad AFR exome

AF:

0.665

Gnomad AMR exome

AF:

0.471

Gnomad ASJ exome

AF:

0.487

Gnomad EAS exome

AF:

0.891

Gnomad FIN exome

AF:

0.428

Gnomad NFE exome

AF:

0.453

Gnomad OTH exome

AF:

0.493

GnomAD4 exome

AF:

0.467

AC:

682703

AN:

1461012

Hom.:

164530

Cov.:

AF XY:

0.466

AC XY:

338470

AN XY:

726852

show subpopulations

African (AFR)

AF:

0.666

AC:

22298

AN:

33478

American (AMR)

AF:

0.476

AC:

21266

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.483

AC:

12622

AN:

26122

East Asian (EAS)

AF:

0.869

AC:

34490

AN:

39694

South Asian (SAS)

AF:

0.442

AC:

38076

AN:

86224

European-Finnish (FIN)

AF:

0.437

AC:

23367

AN:

53412

Middle Eastern (MID)

AF:

0.526

AC:

3030

AN:

5764

European-Non Finnish (NFE)

AF:

0.448

AC:

497978

AN:

1111242

Other (OTH)

AF:

0.490

AC:

29576

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

17765

35530

53295

71060

88825

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15196

30392

45588

60784

75980

<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:

0.526

AC:

80072

AN:

152098

Hom.:

22023

Cov.:

AF XY:

0.524

AC XY:

38992

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.661

AC:

27430

AN:

41468

American (AMR)

AF:

0.479

AC:

7324

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.478

AC:

1660

AN:

3472

East Asian (EAS)

AF:

0.876

AC:

4548

AN:

5190

South Asian (SAS)

AF:

0.452

AC:

2179

AN:

4818

European-Finnish (FIN)

AF:

0.424

AC:

4476

AN:

10562

Middle Eastern (MID)

AF:

0.517

AC:

152

AN:

294

European-Non Finnish (NFE)

AF:

0.454

AC:

30866

AN:

67974

Other (OTH)

AF:

0.501

AC:

1060

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1872

3743

5615

7486

9358

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

700

1400

2100

2800

3500

<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:

0.470

Hom.:

36484

Bravo

AF:

0.538

Asia WGS

AF:

0.634

AC:

2200

AN:

3478

EpiCase

AF:

0.457

EpiControl

AF:

0.452

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Asp743Asp in exon 15 of DNAH5: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 45.4% (3904/8600) o f European American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs1445823). -

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 26, 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. -

not provided

Benign:2

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

-0.87

CADD

Benign

9.4

(source)

DANN

Benign

0.61

PhyloP100

0.073

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over