rs587777501
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP5_Moderate
The NM_021147.5(CCNO):c.961C>T(p.Gln321Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000479 in 1,461,768 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 Likely pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
CCNO
NM_021147.5 stop_gained
NM_021147.5 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 3.83
Genes affected
CCNO (HGNC:18576): (cyclin O) This gene encodes a member of the cyclin protein family, and the encoded protein is involved in regulation of the cell cycle. Disruption of this gene is associated with primary ciliary dyskinesia-19. Alternative splicing results in multiple transcript variants. This gene, which has a previous symbol of UNG2, was erroneously identified as a uracil DNA glycosylase in PubMed ID: 2001396. A later publication, PubMed ID: 8419333, identified this gene's product as a cyclin protein family member. The UNG2 symbol is also used as a specific protein isoform name for the UNG gene (GeneID 7374), so confusion exists in the scientific literature and in some databases for these two genes. [provided by RefSeq, Jul 2014]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0874 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 5-55231467-G-A is Pathogenic according to our data. Variant chr5-55231467-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 139602.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-55231467-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCNO | NM_021147.5 | c.961C>T | p.Gln321Ter | stop_gained | 3/3 | ENST00000282572.5 | |
CCNO | NR_125346.2 | n.1422C>T | non_coding_transcript_exon_variant | 3/3 | |||
CCNO | NR_125347.2 | n.1051C>T | non_coding_transcript_exon_variant | 3/3 | |||
CCNO | NR_125348.1 | n.1025C>T | non_coding_transcript_exon_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCNO | ENST00000282572.5 | c.961C>T | p.Gln321Ter | stop_gained | 3/3 | 1 | NM_021147.5 | P1 | |
CCNO | ENST00000501463.2 | c.*941C>T | 3_prime_UTR_variant, NMD_transcript_variant | 3/3 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461768Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727202
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727202
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
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Cov.:
33
Bravo
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 12, 2022 | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. ClinVar contains an entry for this variant (Variation ID: 139602). This premature translational stop signal has been observed in individual(s) with primary ciliary dyskinesia (PMID: 24747639, 26139845). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln321*) in the CCNO gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 30 amino acid(s) of the CCNO protein. - |
Primary ciliary dyskinesia 29 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 2014 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
D
Vest4
GERP RS
Splicing
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Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at