rs10513155

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.8586G>T(p.Leu2862Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 1,613,654 control chromosomes in the GnomAD database, including 58,738 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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. L2862S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.24 ( 4494 hom., cov: 32)

Exomes 𝑓: 0.27 ( 54244 hom. )

Consequence

DNAH5
NM_001369.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.376

Publications

29 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=0.0048581064).

BP6

Variant 5-13788777-C-A is Benign according to our data. Variant chr5-13788777-C-A is described in ClinVar as Benign. ClinVar VariationId is 178745.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3 link	c.8586G>T	p.Leu2862Phe	missense_variant	Exon 51 of 79	ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5 link	c.8586G>T	p.Leu2862Phe	missense_variant	Exon 51 of 79	1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1 link	c.8541G>T	p.Leu2847Phe	missense_variant	Exon 51 of 79			ENSP00000505288.1

Frequencies

GnomAD3 genomes

AF:

0.237

AC:

36061

AN:

151964

Hom.:

4494

Cov.:

show subpopulations

Gnomad AFR

AF:

0.166

Gnomad AMI

AF:

0.371

Gnomad AMR

AF:

0.263

Gnomad ASJ

AF:

0.328

Gnomad EAS

AF:

0.212

Gnomad SAS

AF:

0.217

Gnomad FIN

AF:

0.207

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.275

Gnomad OTH

AF:

0.259

GnomAD2 exomes

AF:

0.254

AC:

63945

AN:

251304

AF XY:

0.258

show subpopulations

Gnomad AFR exome

AF:

0.160

Gnomad AMR exome

AF:

0.253

Gnomad ASJ exome

AF:

0.334

Gnomad EAS exome

AF:

0.220

Gnomad FIN exome

AF:

0.218

Gnomad NFE exome

AF:

0.280

Gnomad OTH exome

AF:

0.282

GnomAD4 exome

AF:

0.269

AC:

393289

AN:

1461572

Hom.:

54244

Cov.:

AF XY:

0.268

AC XY:

194868

AN XY:

727084

show subpopulations

African (AFR)

AF:

0.169

AC:

5651

AN:

33478

American (AMR)

AF:

0.255

AC:

11392

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.334

AC:

8728

AN:

26126

East Asian (EAS)

AF:

0.181

AC:

7191

AN:

39688

South Asian (SAS)

AF:

0.225

AC:

19370

AN:

86250

European-Finnish (FIN)

AF:

0.221

AC:

11790

AN:

53416

Middle Eastern (MID)

AF:

0.380

AC:

2193

AN:

5768

European-Non Finnish (NFE)

AF:

0.279

AC:

310232

AN:

1111750

Other (OTH)

AF:

0.277

AC:

16742

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

14648

29295

43943

58590

73238

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10282

20564

30846

41128

51410

<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:

0.237

AC:

36063

AN:

152082

Hom.:

4494

Cov.:

AF XY:

0.236

AC XY:

17539

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.166

AC:

6891

AN:

41486

American (AMR)

AF:

0.263

AC:

4016

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.328

AC:

1139

AN:

3472

East Asian (EAS)

AF:

0.212

AC:

1099

AN:

5178

South Asian (SAS)

AF:

0.214

AC:

1029

AN:

4808

European-Finnish (FIN)

AF:

0.207

AC:

2184

AN:

10572

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.275

AC:

18722

AN:

67972

Other (OTH)

AF:

0.256

AC:

542

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1412

2824

4235

5647

7059

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

386

772

1158

1544

1930

<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:

0.271

Hom.:

28768

Bravo

AF:

0.239

TwinsUK

AF:

0.275

AC:

1018

ALSPAC

AF:

0.277

AC:

1068

ESP6500AA

AF:

0.163

AC:

719

ESP6500EA

AF:

0.289

AC:

2482

ExAC

AF:

0.252

AC:

30634

Asia WGS

AF:

0.212

AC:

738

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

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

Leu2862Phe in exon 51 of DNAH5: This variant is not expected to have clinical si gnificance because it has been identified in 28.9% (2482/8600) of European Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs10513155).

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Primary ciliary dyskinesia

Benign:3

Dec 11, 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.

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

Primary ciliary dyskinesia 3

Benign:3

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

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:2

Nov 27, 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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.4

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.15

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.54

MetaRNN

Benign

0.0049

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.5

PhyloP100

-0.38

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.8

REVEL

Benign

0.097

Sift

Benign

0.69

Vest4

0.018

ClinPred

0.0049

GERP RS

4.0

Varity_R

0.057

gMVP

0.43

Mutation Taster

=96/4

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over