rs267607225
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_178452.6(DNAAF1):c.811C>T(p.Arg271Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000547 in 1,461,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
DNAAF1
NM_178452.6 stop_gained
NM_178452.6 stop_gained
Scores
2
4
1
Clinical Significance
Conservation
PhyloP100: 4.43
Genes affected
DNAAF1 (HGNC:30539): (dynein axonemal assembly factor 1) The protein encoded by this gene is cilium-specific and is required for the stability of the ciliary architecture. It is involved in the regulation of microtubule-based cilia and actin-based brush border microvilli. Mutations in this gene are associated with primary ciliary dyskinesia-13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]
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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 16-84159744-C-T is Pathogenic according to our data. Variant chr16-84159744-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 264.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAAF1 | NM_178452.6 | c.811C>T | p.Arg271Ter | stop_gained | 6/12 | ENST00000378553.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF1 | ENST00000378553.10 | c.811C>T | p.Arg271Ter | stop_gained | 6/12 | 1 | NM_178452.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
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33
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251440Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135896
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GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461622Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727124
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GnomAD4 genome ? Cov.: 33
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia 13 Pathogenic:2
Pathogenic, no assertion criteria provided | curation | GeneReviews | Sep 15, 2011 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 2009 | - - |
Primary ciliary dyskinesia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 27, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 264). This premature translational stop signal has been observed in individual(s) with primary ciliary dyskinesia (PMID: 19944400). This variant is present in population databases (rs267607225, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Arg271*) in the DNAAF1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DNAAF1 are known to be pathogenic (PMID: 19944400, 19944405). - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A
Vest4
GERP RS
Splicing
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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