rs1555723797
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Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_145045.5(ODAD3):c.267_268insT(p.Glu90Ter) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,866 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: 30)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
ODAD3
NM_145045.5 frameshift
NM_145045.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.397
Genes affected
ODAD3 (HGNC:28303): (outer dynein arm docking complex subunit 3) This gene encodes a protein containing coiled-coil domains. The encoded protein functions in outer dynein arm assembly and is required for motile cilia function. Mutations in this gene result in primary ciliary dyskinesia. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 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 19-11430997-C-CA is Pathogenic according to our data. Variant chr19-11430997-C-CA is described in ClinVar as [Pathogenic]. Clinvar id is 477980.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ODAD3 | NM_145045.5 | c.267_268insT | p.Glu90Ter | frameshift_variant | 2/13 | ENST00000356392.9 | |
ODAD3 | NM_001302453.1 | c.105_106insT | p.Glu36Ter | frameshift_variant | 2/13 | ||
ODAD3 | NM_001302454.2 | c.267_268insT | p.Glu90Ter | frameshift_variant | 2/11 | ||
ODAD3 | XM_017026241.2 | c.267_268insT | p.Glu90Ter | frameshift_variant | 2/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ODAD3 | ENST00000356392.9 | c.267_268insT | p.Glu90Ter | frameshift_variant | 2/13 | 1 | NM_145045.5 | P2 |
Frequencies
GnomAD3 genomes Cov.: 30
GnomAD3 genomes
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30
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461866Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1AN XY: 727232
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GnomAD4 genome Cov.: 30
GnomAD4 genome
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30
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia 30 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Beijing Key Laboratry for Genetics of Birth Defects, Beijing Children's Hospital | Dec 20, 2020 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Feb 11, 2022 | This sequence change creates a premature translational stop signal (p.Glu90*) in the CCDC151 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CCDC151 are known to be pathogenic (PMID: 25192045). This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 477980). This variant has not been reported in the literature in individuals affected with CCDC151-related conditions. - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -3
Find out detailed SpliceAI scores and Pangolin per-transcript scores at