rs878855036
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_017802.4(DNAAF5):c.2353_2354del(p.Ser785GlnfsTer14) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000684 in 1,461,864 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: 6.8e-7 ( 0 hom. )
Consequence
DNAAF5
NM_017802.4 frameshift
NM_017802.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.74
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]
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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 7-780063-CAG-C is Pathogenic according to our data. Variant chr7-780063-CAG-C is described in ClinVar as [Pathogenic]. Clinvar id is 241202.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAAF5 | NM_017802.4 | c.2353_2354del | p.Ser785GlnfsTer14 | frameshift_variant | 12/13 | ENST00000297440.11 | |
DNAAF5 | XM_024446813.2 | c.2239+4904_2239+4905del | intron_variant | ||||
DNAAF5 | NR_075098.2 | n.2313_2314del | non_coding_transcript_exon_variant | 12/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF5 | ENST00000297440.11 | c.2353_2354del | p.Ser785GlnfsTer14 | frameshift_variant | 12/13 | 1 | NM_017802.4 | P1 | |
DNAAF5 | ENST00000403952.3 | c.628_629del | p.Ser210GlnfsTer14 | frameshift_variant | 5/6 | 1 | |||
DNAAF5 | ENST00000440747.5 | c.1757_1758del | p.Ser587GlnfsTer14 | frameshift_variant | 12/13 | 2 | |||
DNAAF5 | ENST00000461576.1 | n.163_164del | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461864Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727236
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GnomAD4 genome ? Cov.: 33
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Bravo
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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 | Invitae | Feb 29, 2016 | This sequence change deletes 2 nucleotides from exon 12 of the DNAAF5 mRNA (c.2353_2354delAG), causing a frameshift at codon 785. This creates a premature translational stop signal (p.Ser785Glnfs*14) and is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. While this particular variant has not been reported in the literature, truncating variants in DNAAF5 are known to be pathogenic (PMID: 24307375, 25232951). - |
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