rs587777498

Variant names:

• chr5-55233271-CGGGCA-C
• rs587777498
• NM_021147.5:c.248_252delTGCCC

Your query was ambiguous. Multiple possible variants found:

• chr5-55233271-CGGGCA-C
• chr5-55233271-CGGGCA-CGGGCAGGGCA

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1

The NM_021147.5(CCNO):​c.248_252delTGCCC​(p.Leu83ArgfsTer51) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000626 in 1,438,160 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L83L) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000063 (0 hom.)
• Consequence: CCNO NM_021147.5 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.81
• Publications: 4 publications found

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]

CCNO-DT (HGNC:55543): (CCNO divergent transcript)

ACMG classification

Our verdict: Likely_pathogenic. The variant received 8 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNO	NM_021147.5	c.248_252delTGCCC	p.Leu83ArgfsTer51	frameshift_variant	Exon 1 of 3	ENST00000282572.5	NP_066970.3
CCNO	NR_125346.2	n.333_337delTGCCC		non_coding_transcript_exon_variant	Exon 1 of 3
CCNO	NR_125347.2	n.333_337delTGCCC		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNO	ENST00000282572.5	c.248_252delTGCCC	p.Leu83ArgfsTer51	frameshift_variant	Exon 1 of 3	1	NM_021147.5	ENSP00000282572.4
CCNO	ENST00000501463.2	n.248_252delTGCCC		non_coding_transcript_exon_variant	Exon 1 of 3	1		ENSP00000422485.1
CCNO-DT	ENST00000749853.1	n.184+42_184+46delCAGGG		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000626 AC: 9 AN: 1438160 Hom.: 0 AF XY: 0.00000560 AC XY: 4 AN XY: 713672

African (AFR) AF: 0.00 AC: 0 AN: 33260

American (AMR) AF: 0.00 AC: 0 AN: 41358

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25604

East Asian (EAS) AF: 0.00 AC: 0 AN: 38946

South Asian (SAS) AF: 0.00 AC: 0 AN: 83502

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47448

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.00000816 AC: 9 AN: 1102848

Other (OTH) AF: 0.00 AC: 0 AN: 59506

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs587777498; hg19: chr5-54529099; COSMIC: COSV57004297; COSMIC: COSV57004297;