rs759409470
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001364171.2(ODAD1):c.1581+4A>G variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,554,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000015 ( 0 hom. )
Consequence
ODAD1
NM_001364171.2 splice_donor_region, intron
NM_001364171.2 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.9324
1
1
Clinical Significance
Conservation
PhyloP100: 1.99
Genes affected
ODAD1 (HGNC:26560): (outer dynein arm docking complex subunit 1) This gene encodes a coiled-coil domain-containing protein that is a component of the outer dynein arm docking complex in cilia cells. Mutations in this gene may cause primary ciliary dyskinesia 20. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. Scorers claiming Benign: dbscSNV1_ADA.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ODAD1 | NM_001364171.2 | c.1581+4A>G | splice_donor_region_variant, intron_variant | ENST00000674294.1 | |||
ODAD1 | NM_144577.4 | c.1470+4A>G | splice_donor_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ODAD1 | ENST00000674294.1 | c.1581+4A>G | splice_donor_region_variant, intron_variant | NM_001364171.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152108Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000107 AC: 2AN: 186692Hom.: 0 AF XY: 0.0000100 AC XY: 1AN XY: 99950
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GnomAD4 exome AF: 0.0000150 AC: 21AN: 1402652Hom.: 0 Cov.: 36 AF XY: 0.0000101 AC XY: 7AN XY: 693110
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152108Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74298
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 15, 2016 | This variant affects a highly conserved nucleotide within the consensus splice site of intron 13 The majority of introns (73%) have an A at this position (PMID: 9536098). This variant is present in population databases (rs759409470, ExAC 0.002%) but has not been reported in the literature in individuals with a CCDC114-related disease. Algorithms developed to predict the effect of sequence changes on mRNA splicing suggest that this variant may alter mRNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this is a rare intronic change with uncertain impact on splicing. It has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: 4
Find out detailed SpliceAI scores and Pangolin per-transcript scores at