rs745465871
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001256715.2(DNAAF3):c.155_156insT(p.Ser54LeufsTer30) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000105 in 1,614,118 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: 𝑓 0.000033 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Consequence
DNAAF3
NM_001256715.2 frameshift
NM_001256715.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.74
Genes affected
DNAAF3 (HGNC:30492): (dynein axonemal assembly factor 3) The protein encoded by this gene is required for the assembly of axonemal inner and outer dynein arms and plays a role in assembling dynein complexes for transport into cilia. Defects in this gene are a cause of primary ciliary dyskinesia type 2 (CILD2). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]
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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
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Very rare variant in population databases, with high coverage;
PP5
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Variant 19-55165930-C-CA is Pathogenic according to our data. Variant chr19-55165930-C-CA is described in ClinVar as [Pathogenic]. Clinvar id is 454617.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAAF3 | NM_001256715.2 | c.155_156insT | p.Ser54LeufsTer30 | frameshift_variant | 3/12 | ENST00000524407.7 | |
DNAAF3-AS1 | XR_007067344.1 | n.469dup | non_coding_transcript_exon_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF3 | ENST00000524407.7 | c.155_156insT | p.Ser54LeufsTer30 | frameshift_variant | 3/12 | 1 | NM_001256715.2 | A2 | |
DNAAF3-AS1 | ENST00000591665.1 | n.1186+3130dup | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152232Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249398Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135334
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GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461886Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 727248
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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 | Oct 07, 2020 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in DNAAF3 are known to be pathogenic (PMID: 22387996). This variant has not been reported in the literature in individuals with DNAAF3-related conditions. ClinVar contains an entry for this variant (Variation ID: 454617). This variant is present in population databases (rs745465871, ExAC 0.002%). This sequence change creates a premature translational stop signal (p.Ser122Leufs*30) in the DNAAF3 gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at