rs30175

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.12910-11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 1,612,616 control chromosomes in the GnomAD database, including 137,296 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 11943 hom., cov: 32)

Exomes 𝑓: 0.41 ( 125353 hom. )

Consequence

DNAH5
NM_001369.3 intron

Scores

Splicing: ADA: 0.00001917

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.717

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=-0.9).

BP6

Variant 5-13714631-G-A is Benign according to our data. Variant chr5-13714631-G-A is described in ClinVar as Benign. ClinVar VariationId is 163133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3 link	c.12910-11C>T		intron_variant	Intron 74 of 78	ENST00000265104.5	NP_001360.1	Q8TE73

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH5	ENST00000265104.5 link	c.12910-11C>T	intron_variant	Intron 74 of 78	1	NM_001369.3	ENSP00000265104.4	Q8TE73
DNAH5	ENST00000683611.1 link	n.232C>T	non_coding_transcript_exon_variant	Exon 1 of 5
DNAH5	ENST00000681290.1 link	c.12865-11C>T	intron_variant	Intron 74 of 78			ENSP00000505288.1	A0A7P0Z455

Frequencies

GnomAD3 genomes

AF:

0.394

AC:

59889

AN:

151896

Hom.:

11928

Cov.:

show subpopulations

Gnomad AFR

AF:

0.367

Gnomad AMI

AF:

0.438

Gnomad AMR

AF:

0.410

Gnomad ASJ

AF:

0.412

Gnomad EAS

AF:

0.431

Gnomad SAS

AF:

0.450

Gnomad FIN

AF:

0.316

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.411

Gnomad OTH

AF:

0.399

GnomAD2 exomes

AF:

0.411

AC:

102830

AN:

250040

AF XY:

0.414

show subpopulations

Gnomad AFR exome

AF:

0.367

Gnomad AMR exome

AF:

0.439

Gnomad ASJ exome

AF:

0.416

Gnomad EAS exome

AF:

0.412

Gnomad FIN exome

AF:

0.326

Gnomad NFE exome

AF:

0.413

Gnomad OTH exome

AF:

0.415

GnomAD4 exome

AF:

0.413

AC:

603156

AN:

1460600

Hom.:

125353

Cov.:

AF XY:

0.414

AC XY:

300768

AN XY:

726608

show subpopulations

African (AFR)

AF:

0.358

AC:

11981

AN:

33452

American (AMR)

AF:

0.434

AC:

19363

AN:

44644

Ashkenazi Jewish (ASJ)

AF:

0.406

AC:

10602

AN:

26136

East Asian (EAS)

AF:

0.400

AC:

15860

AN:

39638

South Asian (SAS)

AF:

0.453

AC:

39074

AN:

86200

European-Finnish (FIN)

AF:

0.331

AC:

17677

AN:

53364

Middle Eastern (MID)

AF:

0.443

AC:

2391

AN:

5402

European-Non Finnish (NFE)

AF:

0.415

AC:

461246

AN:

1111440

Other (OTH)

AF:

0.414

AC:

24962

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

19488

38976

58465

77953

97441

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14338

28676

43014

57352

71690

<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:

0.394

AC:

59950

AN:

152016

Hom.:

11943

Cov.:

AF XY:

0.390

AC XY:

28945

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.367

AC:

15215

AN:

41450

American (AMR)

AF:

0.410

AC:

6269

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.412

AC:

1428

AN:

3470

East Asian (EAS)

AF:

0.431

AC:

2224

AN:

5162

South Asian (SAS)

AF:

0.450

AC:

2171

AN:

4820

European-Finnish (FIN)

AF:

0.316

AC:

3340

AN:

10566

Middle Eastern (MID)

AF:

0.435

AC:

128

AN:

294

European-Non Finnish (NFE)

AF:

0.411

AC:

27928

AN:

67956

Other (OTH)

AF:

0.402

AC:

848

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1919

3839

5758

7678

9597

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

594

1188

1782

2376

2970

<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:

0.403

Hom.:

17883

Bravo

AF:

0.400

Asia WGS

AF:

0.447

AC:

1556

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

- -

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

12910-11C>T in intron 74 of DNAH5: This variant is not expected to have clinical significance because it has been identified in 42.3% (3635/8600) of European Am erican chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs30175). -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Primary ciliary dyskinesia 3

Benign:3

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 15, 2021

Pars Genome Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

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

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.90

CADD

Benign

1.2

(source)

DANN

Benign

0.48

PhyloP100

0.72

Mutation Taster

=30/70

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000019

dbscSNV1_RF

Benign

0.0

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over