rs3922641

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_StrongBA1

The NM_017802.4(DNAAF5):c.2228G>A(p.Arg743Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 1,613,026 control chromosomes in the GnomAD database, including 306,208 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 31879 hom., cov: 32)

Exomes 𝑓: 0.61 ( 274329 hom. )

Consequence

DNAAF5
NM_017802.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.716

Publications

40 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: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, PanelApp Australia
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=4.737047E-6).

BP6

Variant 7-775151-G-A is Benign according to our data. Variant chr7-775151-G-A is described in ClinVar as Benign. ClinVar VariationId is 260932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

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.2228G>A	p.Arg743Lys	missense	Exon 11 of 13	NP_060272.3
	DNAAF5	NR_075098.2		n.2188G>A		non_coding_transcript_exon	Exon 11 of 13

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DNAAF5	ENST00000297440.11	TSL:1 MANE Select	c.2228G>A	p.Arg743Lys	missense	Exon 11 of 13	ENSP00000297440.6
DNAAF5	ENST00000403952.3	TSL:1	c.503G>A	p.Arg168Lys	missense	Exon 4 of 6	ENSP00000384884.3
DNAAF5	ENST00000852634.1		c.2309G>A	p.Arg770Lys	missense	Exon 12 of 14	ENSP00000522693.1

Frequencies

GnomAD3 genomes

AF:

0.644

AC:

97883

AN:

151928

Hom.:

31830

Cov.:

show subpopulations

Gnomad AFR

AF:

0.705

Gnomad AMI

AF:

0.559

Gnomad AMR

AF:

0.673

Gnomad ASJ

AF:

0.561

Gnomad EAS

AF:

0.625

Gnomad SAS

AF:

0.669

Gnomad FIN

AF:

0.666

Gnomad MID

AF:

0.560

Gnomad NFE

AF:

0.603

Gnomad OTH

AF:

0.650

GnomAD2 exomes

AF:

0.623

AC:

156526

AN:

251100

AF XY:

0.622

show subpopulations

Gnomad AFR exome

AF:

0.703

Gnomad AMR exome

AF:

0.619

Gnomad ASJ exome

AF:

0.582

Gnomad EAS exome

AF:

0.633

Gnomad FIN exome

AF:

0.662

Gnomad NFE exome

AF:

0.602

Gnomad OTH exome

AF:

0.615

GnomAD4 exome

AF:

0.612

AC:

894039

AN:

1460980

Hom.:

274329

Cov.:

AF XY:

0.612

AC XY:

444980

AN XY:

726822

show subpopulations

African (AFR)

AF:

0.716

AC:

23952

AN:

33450

American (AMR)

AF:

0.627

AC:

28022

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.579

AC:

15128

AN:

26126

East Asian (EAS)

AF:

0.605

AC:

24026

AN:

39694

South Asian (SAS)

AF:

0.644

AC:

55581

AN:

86242

European-Finnish (FIN)

AF:

0.662

AC:

35325

AN:

53370

Middle Eastern (MID)

AF:

0.594

AC:

3425

AN:

5766

European-Non Finnish (NFE)

AF:

0.604

AC:

671343

AN:

1111252

Other (OTH)

AF:

0.617

AC:

37237

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

17275

34550

51826

69101

86376

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18306

36612

54918

73224

91530

<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:

0.644

AC:

97980

AN:

152046

Hom.:

31879

Cov.:

AF XY:

0.647

AC XY:

48100

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.705

AC:

29233

AN:

41458

American (AMR)

AF:

0.673

AC:

10271

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.561

AC:

1949

AN:

3472

East Asian (EAS)

AF:

0.625

AC:

3235

AN:

5180

South Asian (SAS)

AF:

0.669

AC:

3224

AN:

4820

European-Finnish (FIN)

AF:

0.666

AC:

7036

AN:

10564

Middle Eastern (MID)

AF:

0.568

AC:

167

AN:

294

European-Non Finnish (NFE)

AF:

0.603

AC:

40976

AN:

67966

Other (OTH)

AF:

0.654

AC:

1380

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1783

3567

5350

7134

8917

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

800

1600

2400

3200

4000

<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:

0.619

Hom.:

83514

Bravo

AF:

0.647

TwinsUK

AF:

0.593

AC:

2199

ALSPAC

AF:

0.624

AC:

2406

ESP6500AA

AF:

0.693

AC:

3053

ESP6500EA

AF:

0.593

AC:

5101

ExAC

AF:

0.621

AC:

75330

Asia WGS

AF:

0.703

AC:

2444

AN:

3478

EpiCase

AF:

0.609

EpiControl

AF:

0.607

ClinVar

ClinVar submissions as Germline

Significance: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 18 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.030

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.14

MetaRNN

Benign

0.0000047

MetaSVM

Benign

-0.93

PhyloP100

0.72

PrimateAI

Benign

0.44

PROVEAN

Benign

1.6

REVEL

Benign

0.072

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.032

MPC

0.16

ClinPred

0.00081

GERP RS

2.8

Varity_R

0.057

gMVP

0.085

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over