rs1555327928
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PP5_Moderate
The NM_018139.3(DNAAF2):c.1433dupG(p.Ser479PhefsTer12) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000484 in 1,445,502 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
DNAAF2
NM_018139.3 frameshift
NM_018139.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.647
Publications
0 publications found
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 10Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen
- primary ciliary dyskinesiaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 10 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
Variant 14-49633716-A-AC is Pathogenic according to our data. Variant chr14-49633716-A-AC is described in ClinVar as Pathogenic. ClinVar VariationId is 525361.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_018139.3. 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 |
|---|---|---|---|---|---|---|---|---|---|
| DNAAF2 | NM_018139.3 | MANE Select | c.1433dupG | p.Ser479PhefsTer12 | frameshift | Exon 1 of 3 | NP_060609.2 | ||
| DNAAF2 | NM_001083908.2 | c.1433dupG | p.Ser479PhefsTer12 | frameshift | Exon 1 of 2 | NP_001077377.1 | |||
| DNAAF2 | NM_001378453.1 | c.-439dupG | 5_prime_UTR | Exon 1 of 2 | NP_001365382.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DNAAF2 | ENST00000298292.13 | TSL:1 MANE Select | c.1433dupG | p.Ser479PhefsTer12 | frameshift | Exon 1 of 3 | ENSP00000298292.8 | ||
| DNAAF2 | ENST00000406043.3 | TSL:1 | c.1433dupG | p.Ser479PhefsTer12 | frameshift | Exon 1 of 2 | ENSP00000384862.3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000484 AC: 7AN: 1445502Hom.: 0 Cov.: 92 AF XY: 0.00000279 AC XY: 2AN XY: 717210 show subpopulations
GnomAD4 exome
AF:
AC:
7
AN:
1445502
Hom.:
Cov.:
92
AF XY:
AC XY:
2
AN XY:
717210
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33010
American (AMR)
AF:
AC:
0
AN:
43462
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25394
East Asian (EAS)
AF:
AC:
0
AN:
39454
South Asian (SAS)
AF:
AC:
0
AN:
85270
European-Finnish (FIN)
AF:
AC:
0
AN:
50878
Middle Eastern (MID)
AF:
AC:
0
AN:
5702
European-Non Finnish (NFE)
AF:
AC:
7
AN:
1102770
Other (OTH)
AF:
AC:
0
AN:
59562
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.489
Heterozygous variant carriers
0
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions as Germline
Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Primary ciliary dyskinesia (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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