14-49633965-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_018139.3(DNAAF2):c.1185G>C(p.Ala395Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 1,527,492 control chromosomes in the GnomAD database, including 415,888 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 39476 hom., cov: 33)

Exomes 𝑓: 0.73 ( 376412 hom. )

Consequence

DNAAF2
NM_018139.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.81

Publications

20 publications found

Variant links:

Genes affected

DNAAF2 (HGNC:20188): (dynein axonemal assembly factor 2) This gene encodes a highly conserved protein involved in the preassembly of dynein arm complexes which power cilia. These complexes are found in some cilia and are assembled in the cytoplasm prior to transport for cilia formation. Mutations in this gene have been associated with primary ciliary dyskinesia. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

DNAAF2 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 10
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAAF2 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=-0.67).

BP6

Variant 14-49633965-C-G is Benign according to our data. Variant chr14-49633965-C-G is described in ClinVar as Benign. ClinVar VariationId is 95891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.81 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
DNAAF2	NM_018139.3 link	c.1185G>C	p.Ala395Ala	synonymous_variant	Exon 1 of 3	ENST00000298292.13	NP_060609.2
DNAAF2	NM_001083908.2 link	c.1185G>C	p.Ala395Ala	synonymous_variant	Exon 1 of 2		NP_001077377.1
DNAAF2	NM_001378453.1 link	c.-687G>C		5_prime_UTR_variant	Exon 1 of 2		NP_001365382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF2	ENST00000298292.13 link	c.1185G>C	p.Ala395Ala	synonymous_variant	Exon 1 of 3	1	NM_018139.3	ENSP00000298292.8
DNAAF2	ENST00000406043.3 link	c.1185G>C	p.Ala395Ala	synonymous_variant	Exon 1 of 2	1		ENSP00000384862.3

Frequencies

GnomAD3 genomes

AF:

0.709

AC:

107811

AN:

151974

Hom.:

39446

Cov.:

show subpopulations

Gnomad AFR

AF:

0.692

Gnomad AMI

AF:

0.828

Gnomad AMR

AF:

0.691

Gnomad ASJ

AF:

0.728

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.534

Gnomad FIN

AF:

0.795

Gnomad MID

AF:

0.728

Gnomad NFE

AF:

0.763

Gnomad OTH

AF:

0.710

GnomAD2 exomes

AF:

0.644

AC:

79450

AN:

123412

AF XY:

0.641

show subpopulations

Gnomad AFR exome

AF:

0.686

Gnomad AMR exome

AF:

0.628

Gnomad ASJ exome

AF:

0.728

Gnomad EAS exome

AF:

0.147

Gnomad FIN exome

AF:

0.774

Gnomad NFE exome

AF:

0.764

Gnomad OTH exome

AF:

0.691

GnomAD4 exome

AF:

0.730

AC:

1004113

AN:

1375408

Hom.:

376412

Cov.:

AF XY:

0.725

AC XY:

491876

AN XY:

678326

show subpopulations

African (AFR)

AF:

0.681

AC:

21152

AN:

31054

American (AMR)

AF:

0.637

AC:

22132

AN:

34720

Ashkenazi Jewish (ASJ)

AF:

0.736

AC:

18139

AN:

24652

East Asian (EAS)

AF:

0.118

AC:

4157

AN:

35306

South Asian (SAS)

AF:

0.548

AC:

42977

AN:

78382

European-Finnish (FIN)

AF:

0.772

AC:

26076

AN:

33758

Middle Eastern (MID)

AF:

0.678

AC:

2940

AN:

4338

European-Non Finnish (NFE)

AF:

0.768

AC:

826629

AN:

1075798

Other (OTH)

AF:

0.695

AC:

39911

AN:

57400

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

17199

34397

51596

68794

85993

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19920

39840

59760

79680

99600

<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:

0.709

AC:

107891

AN:

152084

Hom.:

39476

Cov.:

AF XY:

0.705

AC XY:

52424

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.692

AC:

28721

AN:

41486

American (AMR)

AF:

0.691

AC:

10581

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.728

AC:

2527

AN:

3472

East Asian (EAS)

AF:

0.147

AC:

755

AN:

5146

South Asian (SAS)

AF:

0.533

AC:

2569

AN:

4824

European-Finnish (FIN)

AF:

0.795

AC:

8427

AN:

10594

Middle Eastern (MID)

AF:

0.738

AC:

214

AN:

290

European-Non Finnish (NFE)

AF:

0.763

AC:

51845

AN:

67940

Other (OTH)

AF:

0.709

AC:

1497

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1532

3064

4596

6128

7660

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

808

1616

2424

3232

4040

<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:

0.695

Hom.:

4655

Bravo

AF:

0.700

Asia WGS

AF:

0.405

AC:

1403

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

Ala395Ala in exon 1 of DNAAF2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 81.2% (138/170) of European American chromosomes from a broad population by the 1000 Genomes Projec t (http://www.ncbi.nlm.nih.gov/projects/SNP; dbSNP rs2985686).

Jul 22, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Primary ciliary dyskinesia 10

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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.

Primary ciliary dyskinesia

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Nov 26, 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.

not provided

Benign:2

Nov 09, 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

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.50

(source)

DANN

Benign

0.61

PhyloP100

-1.8

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