rs587777500

Positions:

• chr5-55231501-CG-C

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_021147.5(CCNO):​c.926del​(p.Pro309ArgfsTer18) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCNO NM_021147.5 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.14

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 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 0.121 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 5-55231501-CG-C is Pathogenic according to our data. Variant chr5-55231501-CG-C is described in ClinVar as [Pathogenic]. Clinvar id is 139601.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-55231501-CG-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNO	NM_021147.5	c.926del	p.Pro309ArgfsTer18	frameshift_variant	3/3	ENST00000282572.5	NP_066970.3
CCNO	NR_125346.2	n.1387del		non_coding_transcript_exon_variant	3/3
CCNO	NR_125347.2	n.1016del		non_coding_transcript_exon_variant	3/3
CCNO	NR_125348.1	n.990del		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNO	ENST00000282572.5	c.926del	p.Pro309ArgfsTer18	frameshift_variant	3/3	1	NM_021147.5	ENSP00000282572	P1
CCNO	ENST00000501463.2	c.*906del		3_prime_UTR_variant, NMD_transcript_variant	3/3	1		ENSP00000422485

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Primary ciliary dyskinesia 29 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 01, 2014

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs587777500; hg19: chr5-54527329;