chr5-13931231-C-T

Variant names:

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 (★★).

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: 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=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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3 link	c.71G>A	p.Gly24Glu	missense_variant	Exon 2 of 79	ENST00000265104.5	NP_001360.1	Q8TE73

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5 link	c.71G>A	p.Gly24Glu	missense_variant	Exon 2 of 79	1	NM_001369.3	ENSP00000265104.4		Q8TE73

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

Significance: Benign

Submissions summary: Benign:12

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

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

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

Gly24Glu in exon 2 of DNAH5: This variant is not expected to have clinical signi ficance because it has been identified in 43.7% (1926/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs1530496). -

Primary ciliary dyskinesia

Benign:3

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 01, 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. -

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. -

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

- -

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

- -

Computational scores

Source: dbNSFP v4.3

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

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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