rs757110526

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_017802.4(DNAAF5):c.2024C>A(p.Thr675Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,611,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T675M) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

DNAAF5
NM_017802.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.94

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: Uncertain_significance. The variant received 2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.856

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF5	NM_017802.4 link	c.2024C>A	p.Thr675Lys	missense_variant	Exon 10 of 13	ENST00000297440.11	NP_060272.3	Q86Y56-1B3KPE2
DNAAF5	XM_024446813.2 link	c.2024C>A	p.Thr675Lys	missense_variant	Exon 10 of 12		XP_024302581.1
DNAAF5	NR_075098.2 link	n.1984C>A		non_coding_transcript_exon_variant	Exon 10 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAAF5	ENST00000297440.11 link	c.2024C>A	p.Thr675Lys	missense_variant	Exon 10 of 13	1	NM_017802.4	ENSP00000297440.6	Q86Y56-1
DNAAF5	ENST00000403952.3 link	c.299C>A	p.Thr100Lys	missense_variant	Exon 3 of 6	1		ENSP00000384884.3	E9PGY2
DNAAF5	ENST00000440747.5 link	c.1427C>A	p.Thr476Lys	missense_variant	Exon 10 of 13	2		ENSP00000403165.1	H0Y650

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000821

AC:

AN:

243578

AF XY:

0.0000150

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000917

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1459556

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726186

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.00

AC:

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51466

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111860

Other (OTH)

AF:

0.0000166

AC:

AN:

60244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41460

American (AMR)

AF:

0.0000654

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68044

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000826

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Uncertain:1

Mar 21, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2024C>A (p.T675K) alteration is located in exon 10 (coding exon 10) of the DNAAF5 gene. This alteration results from a C to A substitution at nucleotide position 2024, causing the threonine (T) at amino acid position 675 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Uncertain

0.062

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

T;T

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.83

T;T

M_CAP

Uncertain

0.23

MetaRNN

Pathogenic

0.86

D;D

MetaSVM

Uncertain

-0.24

PhyloP100

3.9

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-5.3

D;D

REVEL

Uncertain

0.38

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.0060

D;D

Polyphen

0.99

D;P

Vest4

0.65

MutPred

0.69

Gain of MoRF binding (P = 0.0194);.;

MVP

0.28

MPC

0.68

ClinPred

1.0

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.78

gMVP

0.60

Mutation Taster

=74/26

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.

rs757110526

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over