rs6554812

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.10140A>G(p.Glu3380Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,612,358 control chromosomes in the GnomAD database, including 68,300 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 7746 hom., cov: 33)

Exomes 𝑓: 0.28 ( 60554 hom. )

Consequence

DNAH5
NM_001369.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0450

Publications

14 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 5-13762863-T-C is Benign according to our data. Variant chr5-13762863-T-C is described in ClinVar as Benign. ClinVar VariationId is 163137.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.045 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3 link	c.10140A>G	p.Glu3380Glu	synonymous_variant	Exon 60 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.10140A>G	p.Glu3380Glu	synonymous_variant	Exon 60 of 79	1	NM_001369.3	ENSP00000265104.4	Q8TE73
DNAH5	ENST00000681290.1 link	c.10095A>G	p.Glu3365Glu	synonymous_variant	Exon 60 of 79			ENSP00000505288.1	A0A7P0Z455
DNAH5	ENST00000504001.3 link	n.648A>G		non_coding_transcript_exon_variant	Exon 5 of 5	5

Frequencies

GnomAD3 genomes

AF:

0.308

AC:

46838

AN:

152010

Hom.:

7726

Cov.:

show subpopulations

Gnomad AFR

AF:

0.368

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.269

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.113

Gnomad SAS

AF:

0.439

Gnomad FIN

AF:

0.442

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.274

Gnomad OTH

AF:

0.280

GnomAD2 exomes

AF:

0.298

AC:

74871

AN:

250966

AF XY:

0.302

show subpopulations

Gnomad AFR exome

AF:

0.367

Gnomad AMR exome

AF:

0.298

Gnomad ASJ exome

AF:

0.210

Gnomad EAS exome

AF:

0.0947

Gnomad FIN exome

AF:

0.424

Gnomad NFE exome

AF:

0.268

Gnomad OTH exome

AF:

0.268

GnomAD4 exome

AF:

0.280

AC:

408259

AN:

1460230

Hom.:

60554

Cov.:

AF XY:

0.284

AC XY:

206515

AN XY:

726510

show subpopulations

African (AFR)

AF:

0.365

AC:

12206

AN:

33428

American (AMR)

AF:

0.294

AC:

13167

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.208

AC:

5437

AN:

26122

East Asian (EAS)

AF:

0.104

AC:

4118

AN:

39684

South Asian (SAS)

AF:

0.434

AC:

37420

AN:

86220

European-Finnish (FIN)

AF:

0.411

AC:

21944

AN:

53372

Middle Eastern (MID)

AF:

0.225

AC:

1294

AN:

5760

European-Non Finnish (NFE)

AF:

0.267

AC:

296021

AN:

1110586

Other (OTH)

AF:

0.276

AC:

16652

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

14779

29558

44337

59116

73895

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9974

19948

29922

39896

49870

<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:

0.308

AC:

46909

AN:

152128

Hom.:

7746

Cov.:

AF XY:

0.315

AC XY:

23440

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.368

AC:

15280

AN:

41494

American (AMR)

AF:

0.269

AC:

4118

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

712

AN:

3470

East Asian (EAS)

AF:

0.113

AC:

587

AN:

5184

South Asian (SAS)

AF:

0.441

AC:

2126

AN:

4822

European-Finnish (FIN)

AF:

0.442

AC:

4673

AN:

10576

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.274

AC:

18600

AN:

67986

Other (OTH)

AF:

0.286

AC:

602

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1668

3336

5004

6672

8340

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

468

936

1404

1872

2340

<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:

0.277

Hom.:

18497

Bravo

AF:

0.291

Asia WGS

AF:

0.329

AC:

1144

AN:

3478

EpiCase

AF:

0.257

EpiControl

AF:

0.257

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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 15, 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 12, 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 specified

Benign:2

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

Glu3380Glu in exon 60 of DNAH5: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 36.3% (1601/4406) of African American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs6554812). -

not provided

Benign:2

Jan 13, 2019

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

BayesDel_noAF

Benign

-0.52

CADD

Benign

1.2

(source)

DANN

Benign

0.61

PhyloP100

0.045

Mutation Taster

=98/2

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