rs150737854

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_018139.3(DNAAF2):c.1406G>A(p.Cys469Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00616 in 1,593,408 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C469S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0049 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0063 ( 87 hom. )

Consequence

DNAAF2
NM_018139.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.309

Publications

10 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: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032324195).

BP6

Variant 14-49633744-C-T is Benign according to our data. Variant chr14-49633744-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 219711.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00494 (752/152336) while in subpopulation SAS AF = 0.0296 (143/4828). AF 95% confidence interval is 0.0257. There are 7 homozygotes in GnomAd4. There are 397 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 7 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018139.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAAF2	NM_018139.3	MANE Select	c.1406G>A	p.Cys469Tyr	missense	Exon 1 of 3	NP_060609.2	Q9NVR5-1
DNAAF2	NM_001083908.2		c.1406G>A	p.Cys469Tyr	missense	Exon 1 of 2	NP_001077377.1	Q9NVR5-2
DNAAF2	NM_001378453.1		c.-466G>A		5_prime_UTR	Exon 1 of 2	NP_001365382.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF2	ENST00000298292.13	TSL:1 MANE Select	c.1406G>A	p.Cys469Tyr	missense	Exon 1 of 3	ENSP00000298292.8	Q9NVR5-1
	DNAAF2	ENST00000406043.3	TSL:1	c.1406G>A	p.Cys469Tyr	missense	Exon 1 of 2	ENSP00000384862.3	Q9NVR5-2

Frequencies

GnomAD3 genomes

AF:

0.00495

AC:

754

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0298

Gnomad FIN

AF:

0.0108

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00559

Gnomad OTH

AF:

0.00669

GnomAD2 exomes

AF:

0.00773

AC:

1796

AN:

232332

AF XY:

0.00886

show subpopulations

Gnomad AFR exome

AF:

0.000864

Gnomad AMR exome

AF:

0.00212

Gnomad ASJ exome

AF:

0.0113

Gnomad EAS exome

AF:

0.0000565

Gnomad FIN exome

AF:

0.00953

Gnomad NFE exome

AF:

0.00625

Gnomad OTH exome

AF:

0.00589

GnomAD4 exome

AF:

0.00629

AC:

9060

AN:

1441072

Hom.:

Cov.:

AF XY:

0.00696

AC XY:

4978

AN XY:

715636

show subpopulations

African (AFR)

AF:

0.000546

AC:

AN:

32954

American (AMR)

AF:

0.00206

AC:

AN:

42676

Ashkenazi Jewish (ASJ)

AF:

0.00980

AC:

246

AN:

25090

East Asian (EAS)

AF:

0.0000506

AC:

AN:

39506

South Asian (SAS)

AF:

0.0260

AC:

2198

AN:

84674

European-Finnish (FIN)

AF:

0.00768

AC:

364

AN:

47404

Middle Eastern (MID)

AF:

0.0122

AC:

AN:

5668

European-Non Finnish (NFE)

AF:

0.00516

AC:

5690

AN:

1103576

Other (OTH)

AF:

0.00647

AC:

385

AN:

59524

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

600

1200

1799

2399

2999

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

224

448

672

896

1120

<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:

0.00494

AC:

752

AN:

152336

Hom.:

Cov.:

AF XY:

0.00533

AC XY:

397

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.000769

AC:

AN:

41588

American (AMR)

AF:

0.00170

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0107

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.0296

AC:

143

AN:

4828

European-Finnish (FIN)

AF:

0.0108

AC:

115

AN:

10628

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00559

AC:

380

AN:

68026

Other (OTH)

AF:

0.00615

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

110

146

183

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00575

Hom.:

Bravo

AF:

0.00379

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.000469

AC:

ESP6500EA

AF:

0.00694

AC:

ExAC

AF:

0.00801

AC:

970

Asia WGS

AF:

0.00895

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

Primary ciliary dyskinesia (2)

not provided (1)

Primary ciliary dyskinesia 10 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.3

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.0022

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.40

MetaRNN

Benign

0.0032

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.69

PhyloP100

0.31

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.8

REVEL

Benign

0.050

Sift

Benign

0.67

Sift4G

Benign

0.086

Polyphen

0.0

Vest4

0.097

MVP

0.092

MPC

0.86

ClinPred

0.0036

GERP RS

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.052

gMVP

0.36

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over