17-41935345-TA-T
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_031421.5(ODAD4):c.245delA(p.Lys82fs) variant causes a frameshift, splice region change. The variant allele was found at a frequency of 0.000075 in 1,613,730 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000074 ( 0 hom. )
Consequence
ODAD4
NM_031421.5 frameshift, splice_region
NM_031421.5 frameshift, splice_region
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.23
Genes affected
ODAD4 (HGNC:25280): (outer dynein arm docking complex subunit 4) This gene encodes a tetratricopeptide repeat domain-containing protein that localizes to ciliary axonmenes and plays a role in the docking of the outer dynein arm to cilia. Mutations in this gene cause severely reduced ciliary motility and the disorder CILD35 (ciliary dyskinesia,primary, 35). Primary ciliary dyskinesia is often associated with recurrent respiratory infections, immotile spermatozoa, and situs inversus; an inversion in left-right body symmetry. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Apr 2017]
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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 17-41935345-TA-T is Pathogenic according to our data. Variant chr17-41935345-TA-T is described in ClinVar as [Pathogenic]. Clinvar id is 869383.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ODAD4 | NM_031421.5 | c.245delA | p.Lys82fs | frameshift_variant, splice_region_variant | 2/12 | ENST00000377540.6 | NP_113609.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ODAD4 | ENST00000377540.6 | c.245delA | p.Lys82fs | frameshift_variant, splice_region_variant | 2/12 | 1 | NM_031421.5 | ENSP00000478589.1 | ||
ODAD4 | ENST00000585530.1 | n.50delA | splice_region_variant, non_coding_transcript_exon_variant | 1/4 | 3 | ENSP00000479460.1 | ||||
ODAD4 | ENST00000591658.5 | n.245delA | splice_region_variant, non_coding_transcript_exon_variant | 2/10 | 5 | ENSP00000477931.1 | ||||
ODAD4 | ENST00000593239.5 | n.245delA | splice_region_variant, non_coding_transcript_exon_variant | 2/6 | 3 | ENSP00000484975.1 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152210Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000644 AC: 16AN: 248454Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134820
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GnomAD4 exome AF: 0.0000739 AC: 108AN: 1461402Hom.: 0 Cov.: 31 AF XY: 0.0000619 AC XY: 45AN XY: 726972
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GnomAD4 genome AF: 0.0000853 AC: 13AN: 152328Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74496
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia 35 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Biology Pathology Center, Lille University Hospital | - | - - |
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