rs72749883

chr5-55232560-G-Achr5-55232560-G-Cchr5-55232560-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_021147.5(CCNO):c.382-14C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,460,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: CCNO NM_021147.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.780

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_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 5-55232560-G-A is Benign according to our data. Variant chr5-55232560-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1633954.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCNO	NM_021147.5	c.382-14C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000282572.5
CCNO	NR_125348.1	n.432C>T		non_coding_transcript_exon_variant	1/2
CCNO	NR_125346.2	n.843-14C>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant
CCNO	NR_125347.2	n.472-14C>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCNO	ENST00000282572.5	c.382-14C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_021147.5	P1
CCNO	ENST00000501463.2	c.*362-14C>T		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000813 AC: 2 AN: 246032 Hom.: 0 AF XY: 0.00000746 AC XY: 1 AN XY: 134056

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000182

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1460418 Hom.: 0 Cov.: 32 AF XY: 0.00000826 AC XY: 6 AN XY: 726486

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000810

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

May 21, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	12
Dann	Benign	0.96

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: rs72749883; hg19: chr5-54528388;