rs6554813

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.10102-29C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,587,034 control chromosomes in the GnomAD database, including 66,638 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.31 ( 7641 hom., cov: 33)

Exomes 𝑓: 0.28 ( 58997 hom. )

Consequence

DNAH5
NM_001369.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.327

Publications

7 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

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 5-13762930-G-A is Benign according to our data. Variant chr5-13762930-G-A is described in ClinVar as Benign. ClinVar VariationId is 257971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3 link	c.10102-29C>T		intron_variant	Intron 59 of 78	ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
DNAH5	ENST00000265104.5 link	c.10102-29C>T	intron_variant	Intron 59 of 78	1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1 link	c.10057-29C>T	intron_variant	Intron 59 of 78			ENSP00000505288.1
DNAH5	ENST00000504001.3 link	n.610-29C>T	intron_variant	Intron 4 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.307

AC:

46581

AN:

151932

Hom.:

7624

Cov.:

show subpopulations

Gnomad AFR

AF:

0.362

Gnomad AMI

AF:

0.157

Gnomad AMR

AF:

0.271

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.112

Gnomad SAS

AF:

0.436

Gnomad FIN

AF:

0.442

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.273

Gnomad OTH

AF:

0.280

GnomAD2 exomes

AF:

0.297

AC:

73526

AN:

247876

AF XY:

0.301

show subpopulations

Gnomad AFR exome

AF:

0.361

Gnomad AMR exome

AF:

0.297

Gnomad ASJ exome

AF:

0.211

Gnomad EAS exome

AF:

0.0929

Gnomad FIN exome

AF:

0.422

Gnomad NFE exome

AF:

0.268

Gnomad OTH exome

AF:

0.267

GnomAD4 exome

AF:

0.279

AC:

400613

AN:

1434982

Hom.:

58997

Cov.:

AF XY:

0.284

AC XY:

203151

AN XY:

715752

show subpopulations

African (AFR)

AF:

0.360

AC:

11870

AN:

32936

American (AMR)

AF:

0.294

AC:

13094

AN:

44564

Ashkenazi Jewish (ASJ)

AF:

0.208

AC:

5414

AN:

26004

East Asian (EAS)

AF:

0.102

AC:

4027

AN:

39500

South Asian (SAS)

AF:

0.431

AC:

36945

AN:

85646

European-Finnish (FIN)

AF:

0.410

AC:

21285

AN:

51972

Middle Eastern (MID)

AF:

0.224

AC:

1283

AN:

5722

European-Non Finnish (NFE)

AF:

0.267

AC:

290310

AN:

1089102

Other (OTH)

AF:

0.275

AC:

16385

AN:

59536

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

13338

26675

40013

53350

66688

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9720

19440

29160

38880

48600

<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:

0.307

AC:

46649

AN:

152052

Hom.:

7641

Cov.:

AF XY:

0.314

AC XY:

23308

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.363

AC:

15042

AN:

41482

American (AMR)

AF:

0.271

AC:

4150

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

712

AN:

3466

East Asian (EAS)

AF:

0.112

AC:

581

AN:

5182

South Asian (SAS)

AF:

0.438

AC:

2110

AN:

4814

European-Finnish (FIN)

AF:

0.442

AC:

4663

AN:

10542

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.273

AC:

18582

AN:

67956

Other (OTH)

AF:

0.283

AC:

597

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1623

3245

4868

6490

8113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

466

932

1398

1864

2330

<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:

0.294

Hom.:

1616

Bravo

AF:

0.290

Asia WGS

AF:

0.324

AC:

1124

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

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:1

PreventionGenetics, part of Exact Sciences

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

-0.85

CADD

Benign

9.6

(source)

DANN

Benign

0.72

PhyloP100

0.33

BranchPoint Hunter

2.0

Mutation Taster

=100/0

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

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