rs118139460

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_017802.4(DNAAF5):c.1432G>A(p.Glu478Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000878 in 1,606,914 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00075 ( 3 hom. )

Consequence

DNAAF5
NM_017802.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.96

Publications

5 publications found

Variant links:

Genes affected

DNAAF5 (HGNC:26013): (dynein axonemal assembly factor 5) The protein encoded by this gene is essential for the preassembly or stability of axonemal dynein arms, and is found only in organisms with motile cilia and flagella. Mutations in this gene are associated with primary ciliary dyskinesia-18, a disorder characterized by abnormalities of motile cilia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2013]

DNAAF5 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 18
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAAF5 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=0.0068619847).

BP6

Variant 7-756956-G-A is Benign according to our data. Variant chr7-756956-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 454853.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00205 (313/152328) while in subpopulation AMR AF = 0.00379 (58/15310). AF 95% confidence interval is 0.00301. There are 3 homozygotes in GnomAd4. There are 140 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017802.4. 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
	DNAAF5	NM_017802.4	MANE Select	c.1432G>A	p.Glu478Lys	missense	Exon 6 of 13	NP_060272.3
	DNAAF5	NR_075098.2		n.1392G>A		non_coding_transcript_exon	Exon 6 of 13

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAAF5	ENST00000297440.11	TSL:1 MANE Select	c.1432G>A	p.Glu478Lys	missense	Exon 6 of 13	ENSP00000297440.6	Q86Y56-1
DNAAF5	ENST00000852634.1		c.1513G>A	p.Glu505Lys	missense	Exon 7 of 14	ENSP00000522693.1
DNAAF5	ENST00000852633.1		c.1432G>A	p.Glu478Lys	missense	Exon 6 of 13	ENSP00000522692.1

Frequencies

GnomAD3 genomes

AF:

0.00206

AC:

313

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.0866

Gnomad AMR

AF:

0.00379

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00103

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00101

AC:

247

AN:

245224

AF XY:

0.000894

show subpopulations

Gnomad AFR exome

AF:

0.00195

Gnomad AMR exome

AF:

0.00247

Gnomad ASJ exome

AF:

0.00320

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000715

Gnomad OTH exome

AF:

0.00264

GnomAD4 exome

AF:

0.000755

AC:

1098

AN:

1454586

Hom.:

Cov.:

AF XY:

0.000720

AC XY:

521

AN XY:

723838

show subpopulations

African (AFR)

AF:

0.00167

AC:

AN:

33468

American (AMR)

AF:

0.00244

AC:

109

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00444

AC:

116

AN:

26110

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46486

Middle Eastern (MID)

AF:

0.00386

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.000630

AC:

700

AN:

1111874

Other (OTH)

AF:

0.00148

AC:

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

130

194

259

324

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.00205

AC:

313

AN:

152328

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

140

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00200

AC:

AN:

41562

American (AMR)

AF:

0.00379

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00432

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00103

AC:

AN:

68034

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

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:

0.00111

Hom.:

Bravo

AF:

0.00234

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000874

AC:

106

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00142

EpiControl

AF:

0.00107

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Primary ciliary dyskinesia (2)

Primary ciliary dyskinesia 18 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.029

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.78

M_CAP

Benign

0.0065

MetaRNN

Benign

0.0069

MetaSVM

Benign

-0.99

PhyloP100

2.0

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.79

REVEL

Benign

0.089

Sift

Benign

0.19

Sift4G

Benign

0.22

Polyphen

0.60

Vest4

0.33

MVP

0.048

MPC

0.21

ClinPred

0.0093

GERP RS

2.4

Varity_R

0.044

gMVP

0.35

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

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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