rs200327783

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001378453.1(DNAAF2):c.-455C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000759 in 1,594,842 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00079 ( 4 hom. )

Consequence

DNAAF2
NM_001378453.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: -0.480

Publications

1 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0070435107).

BP6

Variant 14-49633733-G-A is Benign according to our data. Variant chr14-49633733-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 216703.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000486 (74/152274) while in subpopulation SAS AF = 0.00145 (7/4826). AF 95% confidence interval is 0.000716. There are 0 homozygotes in GnomAd4. There are 33 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 4 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378453.1. 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.1417C>T	p.Arg473Trp	missense	Exon 1 of 3	NP_060609.2	Q9NVR5-1
DNAAF2	NM_001378453.1		c.-455C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	NP_001365382.1
DNAAF2	NM_001083908.2		c.1417C>T	p.Arg473Trp	missense	Exon 1 of 2	NP_001077377.1	Q9NVR5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF2	ENST00000298292.13	TSL:1 MANE Select	c.1417C>T	p.Arg473Trp	missense	Exon 1 of 3	ENSP00000298292.8	Q9NVR5-1
	DNAAF2	ENST00000406043.3	TSL:1	c.1417C>T	p.Arg473Trp	missense	Exon 1 of 2	ENSP00000384862.3	Q9NVR5-2

Frequencies

GnomAD3 genomes

AF:

0.000486

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000897

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000505

AC:

119

AN:

235636

AF XY:

0.000552

show subpopulations

Gnomad AFR exome

AF:

0.000264

Gnomad AMR exome

AF:

0.0000910

Gnomad ASJ exome

AF:

0.000113

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000546

Gnomad OTH exome

AF:

0.000176

GnomAD4 exome

AF:

0.000787

AC:

1136

AN:

1442568

Hom.:

Cov.:

AF XY:

0.000812

AC XY:

581

AN XY:

715828

show subpopulations

African (AFR)

AF:

0.000273

AC:

AN:

33008

American (AMR)

AF:

0.0000695

AC:

AN:

43186

Ashkenazi Jewish (ASJ)

AF:

0.0000793

AC:

AN:

25206

East Asian (EAS)

AF:

0.00

AC:

AN:

39466

South Asian (SAS)

AF:

0.00170

AC:

144

AN:

84900

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49010

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.000855

AC:

943

AN:

1102582

Other (OTH)

AF:

0.000571

AC:

AN:

59524

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

157

235

314

392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

176

220

<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:

0.000486

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0000962

AC:

AN:

41566

American (AMR)

AF:

0.0000653

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00145

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000897

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000366

Hom.:

Bravo

AF:

0.000355

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000237

AC:

ESP6500EA

AF:

0.00130

AC:

ExAC

AF:

0.000504

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Primary ciliary dyskinesia (2)

Primary ciliary dyskinesia 10 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0081

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0086

LIST_S2

Benign

0.53

M_CAP

Benign

0.011

MetaRNN

Benign

0.0070

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.6

PhyloP100

-0.48

PrimateAI

Benign

0.32

PROVEAN

Benign

-2.0

REVEL

Benign

0.022

Sift

Uncertain

0.023

Sift4G

Uncertain

0.030

Polyphen

0.0

Vest4

0.10

MVP

0.20

MPC

0.72

ClinPred

0.069

GERP RS

-4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.044

gMVP

0.40

Mutation Taster

=99/1

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

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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