NM_001256715.2:c.1164-14C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001256715.2(DNAAF3):c.1164-14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0533 in 1,612,500 control chromosomes in the GnomAD database, including 6,897 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.068 ( 808 hom., cov: 33)

Exomes 𝑓: 0.052 ( 6089 hom. )

Consequence

DNAAF3
NM_001256715.2 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.275

Publications

5 publications found

Variant links:

Genes affected

DNAAF3 (HGNC:30492): (dynein axonemal assembly factor 3) The protein encoded by this gene is required for the assembly of axonemal inner and outer dynein arms and plays a role in assembling dynein complexes for transport into cilia. Defects in this gene are a cause of primary ciliary dyskinesia type 2 (CILD2). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

DNAAF3 links:

ENSG00000267110 (HGNC:):

ENSG00000267110 links:

DNAAF3-AS1 (HGNC:55292): (DNAAF3 antisense RNA 1)

DNAAF3-AS1 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 (REVEL=0.005).

BP6

Variant 19-55159621-G-A is Benign according to our data. Variant chr19-55159621-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257682.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF3	NM_001256715.2 link	c.1164-14C>T		intron_variant	Intron 10 of 11	ENST00000524407.7	NP_001243644.1	Q8N9W5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF3	ENST00000524407.7 link	c.1164-14C>T		intron_variant	Intron 10 of 11	1	NM_001256715.2	ENSP00000432046.3		Q8N9W5-1
ENSG00000267110	ENST00000587871.1 link	n.147-14C>T		intron_variant	Intron 2 of 8	5		ENSP00000473050.1		M0R381

Frequencies

GnomAD3 genomes

AF:

0.0677

AC:

10299

AN:

152146

Hom.:

797

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0663

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.215

Gnomad ASJ

AF:

0.0352

Gnomad EAS

AF:

0.221

Gnomad SAS

AF:

0.151

Gnomad FIN

AF:

0.0277

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0266

Gnomad OTH

AF:

0.0775

GnomAD2 exomes

AF:

0.107

AC:

26410

AN:

246984

AF XY:

0.0965

show subpopulations

Gnomad AFR exome

AF:

0.0684

Gnomad AMR exome

AF:

0.371

Gnomad ASJ exome

AF:

0.0332

Gnomad EAS exome

AF:

0.220

Gnomad FIN exome

AF:

0.0309

Gnomad NFE exome

AF:

0.0272

Gnomad OTH exome

AF:

0.0803

GnomAD4 exome

AF:

0.0518

AC:

75646

AN:

1460236

Hom.:

6089

Cov.:

AF XY:

0.0525

AC XY:

38153

AN XY:

726356

show subpopulations

African (AFR)

AF:

0.0674

AC:

2254

AN:

33454

American (AMR)

AF:

0.357

AC:

15871

AN:

44422

Ashkenazi Jewish (ASJ)

AF:

0.0351

AC:

914

AN:

26022

East Asian (EAS)

AF:

0.242

AC:

9597

AN:

39688

South Asian (SAS)

AF:

0.134

AC:

11485

AN:

85940

European-Finnish (FIN)

AF:

0.0327

AC:

1743

AN:

53240

Middle Eastern (MID)

AF:

0.0421

AC:

243

AN:

5768

European-Non Finnish (NFE)

AF:

0.0269

AC:

29897

AN:

1111392

Other (OTH)

AF:

0.0604

AC:

3642

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

3867

7735

11602

15470

19337

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1548

3096

4644

6192

7740

<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:

0.0679

AC:

10332

AN:

152264

Hom.:

808

Cov.:

AF XY:

0.0727

AC XY:

5413

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0663

AC:

2754

AN:

41534

American (AMR)

AF:

0.216

AC:

3301

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0352

AC:

122

AN:

3470

East Asian (EAS)

AF:

0.222

AC:

1147

AN:

5164

South Asian (SAS)

AF:

0.151

AC:

728

AN:

4830

European-Finnish (FIN)

AF:

0.0277

AC:

294

AN:

10626

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0266

AC:

1813

AN:

68034

Other (OTH)

AF:

0.0781

AC:

165

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

450

900

1349

1799

2249

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

240

360

480

600

<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:

0.0476

Hom.:

Bravo

AF:

0.0829

Asia WGS

AF:

0.199

AC:

690

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Familial Hypertrophic Cardiomyopathy with Wolff-Parkinson-White Syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dilated Cardiomyopathy, Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely 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

- -

Hypertrophic cardiomyopathy

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Familial restrictive cardiomyopathy

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely 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

-0.72

CADD

Benign

5.6

(source)

DANN

Benign

0.90

PhyloP100

-0.28

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

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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