5-55233261-T-TGGGCCGGGCC
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_021147.5(CCNO):c.262_263insGGCCCGGCCC(p.Gln88ArgfsTer51) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000881 in 1,589,378 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000090 ( 0 hom. )
Consequence
CCNO
NM_021147.5 frameshift
NM_021147.5 frameshift
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.939
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 Pathogenic. Variant got 10 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;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCNO | NM_021147.5 | c.262_263insGGCCCGGCCC | p.Gln88ArgfsTer51 | frameshift_variant | 1/3 | ENST00000282572.5 | |
CCNO | NR_125346.2 | n.347_348insGGCCCGGCCC | non_coding_transcript_exon_variant | 1/3 | |||
CCNO | NR_125347.2 | n.347_348insGGCCCGGCCC | non_coding_transcript_exon_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCNO | ENST00000282572.5 | c.262_263insGGCCCGGCCC | p.Gln88ArgfsTer51 | frameshift_variant | 1/3 | 1 | NM_021147.5 | P1 | |
CCNO | ENST00000501463.2 | c.262_263insGGCCCGGCCC | p.Gln88ArgfsTer107 | frameshift_variant, NMD_transcript_variant | 1/3 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152094Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000493 AC: 1AN: 202796Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 110912
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GnomAD4 exome AF: 0.00000904 AC: 13AN: 1437284Hom.: 0 Cov.: 32 AF XY: 0.00000982 AC XY: 7AN XY: 713126
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152094Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74308
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at