Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_017802.4(DNAAF5):c.1056C>T(p.Leu352Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00363 in 1,614,096 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0093 ( 16 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 30 hom. )

Consequence

DNAAF5
NM_017802.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.826

Publications

0 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: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
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 -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.043).

BP6

Variant 7-754620-C-T is Benign according to our data. Variant chr7-754620-C-T is described in ClinVar as Benign. ClinVar VariationId is 260921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.826 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00933 (1421/152282) while in subpopulation AFR AF = 0.0212 (880/41556). AF 95% confidence interval is 0.02. There are 16 homozygotes in GnomAd4. There are 634 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 16 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF5	NM_017802.4	MANE Select	c.1056C>T	p.Leu352Leu	synonymous	Exon 5 of 13	NP_060272.3
	DNAAF5	NR_075098.2		n.1016C>T		non_coding_transcript_exon	Exon 5 of 13

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DNAAF5	ENST00000297440.11	TSL:1 MANE Select	c.1056C>T	p.Leu352Leu	synonymous	Exon 5 of 13	ENSP00000297440.6
DNAAF5	ENST00000440747.5	TSL:2	c.459C>T	p.Leu153Leu	synonymous	Exon 5 of 13	ENSP00000403165.1
DNAAF5	ENST00000437419.5	TSL:5	c.372C>T	p.Leu124Leu	synonymous	Exon 4 of 5	ENSP00000410788.1

Frequencies

GnomAD3 genomes

AF:

0.00934

AC:

1421

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0212

Gnomad AMI

AF:

0.0866

Gnomad AMR

AF:

0.00857

Gnomad ASJ

AF:

0.0185

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.000660

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00332

Gnomad OTH

AF:

0.00813

GnomAD2 exomes

AF:

0.00476

AC:

1195

AN:

251074

AF XY:

0.00422

show subpopulations

Gnomad AFR exome

AF:

0.0232

Gnomad AMR exome

AF:

0.00709

Gnomad ASJ exome

AF:

0.0146

Gnomad EAS exome

AF:

0.000598

Gnomad FIN exome

AF:

0.000601

Gnomad NFE exome

AF:

0.00291

Gnomad OTH exome

AF:

0.00767

GnomAD4 exome

AF:

0.00304

AC:

4446

AN:

1461814

Hom.:

Cov.:

AF XY:

0.00295

AC XY:

2145

AN XY:

727196

show subpopulations

African (AFR)

AF:

0.0208

AC:

695

AN:

33480

American (AMR)

AF:

0.00702

AC:

314

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0154

AC:

402

AN:

26136

East Asian (EAS)

AF:

0.000453

AC:

AN:

39700

South Asian (SAS)

AF:

0.000626

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.000506

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.0113

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00225

AC:

2499

AN:

1111960

Other (OTH)

AF:

0.00616

AC:

372

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

243

487

730

974

1217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

208

312

416

520

<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:

0.00933

AC:

1421

AN:

152282

Hom.:

Cov.:

AF XY:

0.00852

AC XY:

634

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0212

AC:

880

AN:

41556

American (AMR)

AF:

0.00856

AC:

131

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0185

AC:

AN:

3468

East Asian (EAS)

AF:

0.000579

AC:

AN:

5182

South Asian (SAS)

AF:

0.000829

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000660

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00332

AC:

226

AN:

68026

Other (OTH)

AF:

0.00805

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

138

206

275

344

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:

0.00637

Hom.:

Bravo

AF:

0.0106

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Primary ciliary dyskinesia (2)

not specified (1)

Primary ciliary dyskinesia 18 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.67

(source)

DANN

Benign

0.60

PhyloP100

-0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over