rs1555327928
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_018139.3(DNAAF2):c.1433dupG(p.Ser479fs) 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
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 14-49633716-A-AC is Pathogenic according to our data. Variant chr14-49633716-A-AC is described in ClinVar as [Pathogenic]. Clinvar id is 525361.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNAAF2 | NM_018139.3 | c.1433dupG | p.Ser479fs | frameshift_variant | 1/3 | ENST00000298292.13 | NP_060609.2 | |
DNAAF2 | NM_001083908.2 | c.1433dupG | p.Ser479fs | frameshift_variant | 1/2 | NP_001077377.1 | ||
DNAAF2 | NM_001378453.1 | c.-439dupG | 5_prime_UTR_variant | 1/2 | NP_001365382.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNAAF2 | ENST00000298292.13 | c.1433dupG | p.Ser479fs | frameshift_variant | 1/3 | 1 | NM_018139.3 | ENSP00000298292.8 | ||
DNAAF2 | ENST00000406043.3 | c.1433dupG | p.Ser479fs | frameshift_variant | 1/2 | 1 | ENSP00000384862.3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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33
GnomAD4 exome AF: 0.00000484 AC: 7AN: 1445502Hom.: 0 Cov.: 92 AF XY: 0.00000279 AC XY: 2AN XY: 717210
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GnomAD4 genome Cov.: 33
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33
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 17, 2023 | This sequence change creates a premature translational stop signal (p.Ser479Phefs*12) in the DNAAF2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DNAAF2 are known to be pathogenic (PMID: 19052621, 24498942). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DNAAF2-related conditions. ClinVar contains an entry for this variant (Variation ID: 525361). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at