5-55231152-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021147.5(CCNO):c.*223A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0197 in 565,658 control chromosomes in the GnomAD database, including 373 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (115 hom., cov: 33)
  • Exomes 𝑓: 0.020 (258 hom.)
• Consequence: CCNO NM_021147.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0930

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 5-55231152-T-C is Benign according to our data. Variant chr5-55231152-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1198050.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCNO	NM_021147.5	c.*223A>G		3_prime_UTR_variant	3/3	ENST00000282572.5
CCNO	NR_125346.2	n.1737A>G		non_coding_transcript_exon_variant	3/3
CCNO	NR_125347.2	n.1366A>G		non_coding_transcript_exon_variant	3/3
CCNO	NR_125348.1	n.1340A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCNO	ENST00000282572.5	c.*223A>G		3_prime_UTR_variant	3/3	1	NM_021147.5	P1
CCNO	ENST00000501463.2	c.*1256A>G		3_prime_UTR_variant, NMD_transcript_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.0198 AC: 3008 AN: 152106 Hom.: 115 Cov.: 33

Gnomad AFR AF: 0.00456

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0899

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0176

Gnomad FIN AF: 0.0140

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0170

Gnomad OTH AF: 0.0186

GnomAD4 exome AF: 0.0197 AC: 8139 AN: 413434 Hom.: 258 Cov.: 5 AF XY: 0.0190 AC XY: 4068 AN XY: 214632

Gnomad4 AFR exome AF: 0.00385

Gnomad4 AMR exome AF: 0.144

Gnomad4 ASJ exome AF: 0.00385

Gnomad4 EAS exome AF: 0.0000350

Gnomad4 SAS exome AF: 0.0181

Gnomad4 FIN exome AF: 0.0129

Gnomad4 NFE exome AF: 0.0161

Gnomad4 OTH exome AF: 0.0207

GnomAD4 genome AF: 0.0198 AC: 3010 AN: 152224 Hom.: 115 Cov.: 33 AF XY: 0.0210 AC XY: 1563 AN XY: 74422

Gnomad4 AFR AF: 0.00455

Gnomad4 AMR AF: 0.0901

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0172

Gnomad4 FIN AF: 0.0140

Gnomad4 NFE AF: 0.0170

Gnomad4 OTH AF: 0.0184

Alfa AF: 0.0202 Hom.: 26

Bravo AF: 0.0269

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 24, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.5
Dann	Benign	0.47

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: rs76296175; hg19: chr5-54526980;