14-49634021-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018139.3(DNAAF2):c.1129G>A(p.Gly377Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,370,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign 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. G377R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

DNAAF2
NM_018139.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.398

Publications

0 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen
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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.037669092).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
DNAAF2	NM_018139.3 link	c.1129G>A	p.Gly377Ser	missense_variant	Exon 1 of 3	ENST00000298292.13	NP_060609.2
DNAAF2	NM_001083908.2 link	c.1129G>A	p.Gly377Ser	missense_variant	Exon 1 of 2		NP_001077377.1
DNAAF2	NM_001378453.1 link	c.-743G>A		upstream_gene_variant			NP_001365382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF2	ENST00000298292.13 link	c.1129G>A	p.Gly377Ser	missense_variant	Exon 1 of 3	1	NM_018139.3	ENSP00000298292.8
DNAAF2	ENST00000406043.3 link	c.1129G>A	p.Gly377Ser	missense_variant	Exon 1 of 2	1		ENSP00000384862.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

115020

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000146

AC:

AN:

1370450

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

675624

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30584

American (AMR)

AF:

0.00

AC:

AN:

33524

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23960

East Asian (EAS)

AF:

0.00

AC:

AN:

35082

South Asian (SAS)

AF:

0.00

AC:

AN:

76852

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36112

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4248

European-Non Finnish (NFE)

AF:

0.00000186

AC:

AN:

1072938

Other (OTH)

AF:

0.00

AC:

AN:

57150

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Uncertain:1

Mar 30, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1129G>A (p.G377S) alteration is located in exon 1 (coding exon 1) of the DNAAF2 gene. This alteration results from a G to A substitution at nucleotide position 1129, causing the glycine (G) at amino acid position 377 to be replaced by a serine (S). 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

Benign

0.093

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

7.3

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0012

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.55

T;T

M_CAP

Benign

0.041

MetaRNN

Benign

0.038

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.94

L;L

PhyloP100

-0.40

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.43

N;N

REVEL

Benign

0.014

Sift

Benign

0.19

T;T

Sift4G

Benign

0.33

T;T

Polyphen

0.0040

B;B

Vest4

0.041

MutPred

0.29

Gain of phosphorylation at G377 (P = 0.0235);Gain of phosphorylation at G377 (P = 0.0235);

MVP

0.14

MPC

0.51

ClinPred

0.081

GERP RS

-1.5

Varity_R

0.058

gMVP

0.32

Mutation Taster

=96/4

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over