rs577796590

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_018139.3(DNAAF2):c.20C>T(p.Ser7Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000332 in 1,562,184 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00016 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00035 ( 9 hom. )

Consequence

DNAAF2
NM_018139.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: 3.15

Publications

2 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=0.009665161).

BP6

Variant 14-49635130-G-A is Benign according to our data. Variant chr14-49635130-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 216704.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000157 (24/152386) while in subpopulation SAS AF = 0.00455 (22/4830). AF 95% confidence interval is 0.00308. There are 1 homozygotes in GnomAd4. There are 19 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 9 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF2	NM_018139.3	MANE Select	c.20C>T	p.Ser7Phe	missense	Exon 1 of 3	NP_060609.2	Q9NVR5-1
	DNAAF2	NM_001083908.2		c.20C>T	p.Ser7Phe	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.20C>T	p.Ser7Phe	missense	Exon 1 of 3	ENSP00000298292.8	Q9NVR5-1
	DNAAF2	ENST00000406043.3	TSL:1	c.20C>T	p.Ser7Phe	missense	Exon 1 of 2	ENSP00000384862.3	Q9NVR5-2

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152268

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000897

AC:

146

AN:

162756

AF XY:

0.00130

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000843

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000110

Gnomad OTH exome

AF:

0.000661

GnomAD4 exome

AF:

0.000350

AC:

494

AN:

1409798

Hom.:

Cov.:

AF XY:

0.000528

AC XY:

368

AN XY:

696660

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32112

American (AMR)

AF:

0.0000807

AC:

AN:

37158

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25314

East Asian (EAS)

AF:

0.00

AC:

AN:

36548

South Asian (SAS)

AF:

0.00538

AC:

431

AN:

80056

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48696

Middle Eastern (MID)

AF:

0.00265

AC:

AN:

5660

European-Non Finnish (NFE)

AF:

0.0000212

AC:

AN:

1085826

Other (OTH)

AF:

0.000377

AC:

AN:

58428

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

109

146

182

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.000157

AC:

AN:

152386

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74520

show subpopulations

African (AFR)

AF:

0.0000240

AC:

AN:

41604

American (AMR)

AF:

0.00

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00455

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

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:

0.000170

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.000849

AC:

Asia WGS

AF:

0.000577

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 (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0092

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.79

M_CAP

Benign

0.010

MetaRNN

Benign

0.0097

MetaSVM

Benign

-0.97

MutationAssessor

Benign

2.0

PhyloP100

3.2

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.087

Sift

Benign

0.050

Sift4G

Uncertain

0.0090

Polyphen

0.98

Vest4

0.25

MutPred

0.24

Loss of phosphorylation at S7 (P = 0.0051)

MVP

0.73

MPC

1.5

ClinPred

0.16

GERP RS

5.3

PromoterAI

0.043

Neutral

(source)

Varity_R

0.26

gMVP

0.32

Mutation Taster

=95/5

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