rs2985685

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_018139.3(DNAAF2):c.498C>T(p.Ala166Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 1,606,680 control chromosomes in the GnomAD database, including 422,825 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 34105 hom., cov: 35)

Exomes 𝑓: 0.72 ( 388720 hom. )

Consequence

DNAAF2
NM_018139.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.913

Publications

18 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 14-49634652-G-A is Benign according to our data. Variant chr14-49634652-G-A is described in ClinVar as Benign. ClinVar VariationId is 95894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.913 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF2	NM_018139.3 link	c.498C>T	p.Ala166Ala	synonymous_variant	Exon 1 of 3	ENST00000298292.13	NP_060609.2	Q9NVR5-1
DNAAF2	NM_001083908.2 link	c.498C>T	p.Ala166Ala	synonymous_variant	Exon 1 of 2		NP_001077377.1	Q9NVR5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF2	ENST00000298292.13 link	c.498C>T	p.Ala166Ala	synonymous_variant	Exon 1 of 3	1	NM_018139.3	ENSP00000298292.8		Q9NVR5-1
DNAAF2	ENST00000406043.3 link	c.498C>T	p.Ala166Ala	synonymous_variant	Exon 1 of 2	1		ENSP00000384862.3		Q9NVR5-2

Frequencies

GnomAD3 genomes

AF:

0.651

AC:

98942

AN:

152076

Hom.:

34092

Cov.:

show subpopulations

Gnomad AFR

AF:

0.495

Gnomad AMI

AF:

0.827

Gnomad AMR

AF:

0.661

Gnomad ASJ

AF:

0.712

Gnomad EAS

AF:

0.148

Gnomad SAS

AF:

0.533

Gnomad FIN

AF:

0.795

Gnomad MID

AF:

0.690

Gnomad NFE

AF:

0.761

Gnomad OTH

AF:

0.673

GnomAD2 exomes

AF:

0.646

AC:

153188

AN:

237064

AF XY:

0.650

show subpopulations

Gnomad AFR exome

AF:

0.489

Gnomad AMR exome

AF:

0.603

Gnomad ASJ exome

AF:

0.717

Gnomad EAS exome

AF:

0.152

Gnomad FIN exome

AF:

0.778

Gnomad NFE exome

AF:

0.762

Gnomad OTH exome

AF:

0.690

GnomAD4 exome

AF:

0.720

AC:

1047179

AN:

1454488

Hom.:

388720

Cov.:

AF XY:

0.716

AC XY:

518273

AN XY:

723902

show subpopulations

African (AFR)

AF:

0.485

AC:

16225

AN:

33474

American (AMR)

AF:

0.612

AC:

27363

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.720

AC:

18808

AN:

26124

East Asian (EAS)

AF:

0.122

AC:

4827

AN:

39682

South Asian (SAS)

AF:

0.547

AC:

47187

AN:

86250

European-Finnish (FIN)

AF:

0.774

AC:

36001

AN:

46496

Middle Eastern (MID)

AF:

0.652

AC:

3760

AN:

5766

European-Non Finnish (NFE)

AF:

0.766

AC:

852040

AN:

1111682

Other (OTH)

AF:

0.679

AC:

40968

AN:

60308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

20461

40922

61382

81843

102304

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20150

40300

60450

80600

100750

<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:

0.651

AC:

99006

AN:

152192

Hom.:

34105

Cov.:

AF XY:

0.648

AC XY:

48225

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.495

AC:

20562

AN:

41524

American (AMR)

AF:

0.661

AC:

10112

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.712

AC:

2472

AN:

3472

East Asian (EAS)

AF:

0.148

AC:

765

AN:

5168

South Asian (SAS)

AF:

0.532

AC:

2569

AN:

4826

European-Finnish (FIN)

AF:

0.795

AC:

8444

AN:

10618

Middle Eastern (MID)

AF:

0.701

AC:

206

AN:

294

European-Non Finnish (NFE)

AF:

0.761

AC:

51701

AN:

67966

Other (OTH)

AF:

0.673

AC:

1422

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1676

3352

5029

6705

8381

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

770

1540

2310

3080

3850

<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:

0.725

Hom.:

12498

Bravo

AF:

0.633

Asia WGS

AF:

0.393

AC:

1367

AN:

3478

EpiCase

AF:

0.755

EpiControl

AF:

0.765

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Ala166Ala 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 47.4% (1842/3888) o f African American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2985685). -

Mar 06, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia 10

Benign:3

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

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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. -

Primary ciliary dyskinesia

Benign:2

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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Sep 13, 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

-0.45

CADD

Benign

7.7

(source)

DANN

Benign

0.91

PhyloP100

0.91

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