5-55232565-G-C

Variant names:

• chr5-55232565-G-C
• rs334892
• NM_021147.5:c.382-19C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000282572.5(CCNO):​c.382-19C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,611,804 control chromosomes in the GnomAD database, including 22,099 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2352 hom., cov: 33)
  • Exomes 𝑓: 0.16 (19747 hom.)
• Consequence: CCNO ENST00000282572.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0260
• Publications: 7 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 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 29

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen, Ambry Genetics
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 5-55232565-G-C is Benign according to our data. Variant chr5-55232565-G-C is described in ClinVar as Benign. ClinVar VariationId is 261408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000282572.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNO	NM_021147.5	MANE Select	c.382-19C>G		intron	N/A	NP_066970.3
	CCNO	NR_125348.1		n.427C>G		non_coding_transcript_exon	Exon 1 of 2
	CCNO	NR_125346.2		n.843-19C>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNO	ENST00000282572.5	TSL:1 MANE Select	c.382-19C>G		intron	N/A	ENSP00000282572.4
	CCNO	ENST00000501463.2	TSL:1	n.*362-19C>G		intron	N/A	ENSP00000422485.1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26671 AN: 152142 Hom.: 2351 Cov.: 33

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.176

GnomAD2 exomes AF: 0.177 AC: 43588 AN: 245704 AF XY: 0.172

Gnomad AFR exome AF: 0.193

Gnomad AMR exome AF: 0.213

Gnomad ASJ exome AF: 0.118

Gnomad EAS exome AF: 0.179

Gnomad FIN exome AF: 0.263

Gnomad NFE exome AF: 0.160

Gnomad OTH exome AF: 0.170

GnomAD4 exome AF: 0.162 AC: 235971 AN: 1459544 Hom.: 19747 Cov.: 33 AF XY: 0.161 AC XY: 116545 AN XY: 726090

African (AFR) AF: 0.199 AC: 6640 AN: 33442

American (AMR) AF: 0.206 AC: 9190 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 3063 AN: 26116

East Asian (EAS) AF: 0.174 AC: 6920 AN: 39690

South Asian (SAS) AF: 0.147 AC: 12657 AN: 86202

European-Finnish (FIN) AF: 0.261 AC: 13707 AN: 52562

Middle Eastern (MID) AF: 0.116 AC: 654 AN: 5644

European-Non Finnish (NFE) AF: 0.156 AC: 173648 AN: 1110922

Other (OTH) AF: 0.157 AC: 9492 AN: 60310

GnomAD4 genome AF: 0.175 AC: 26694 AN: 152260 Hom.: 2352 Cov.: 33 AF XY: 0.180 AC XY: 13422 AN XY: 74454

African (AFR) AF: 0.193 AC: 8011 AN: 41566

American (AMR) AF: 0.178 AC: 2717 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 386 AN: 3468

East Asian (EAS) AF: 0.180 AC: 931 AN: 5176

South Asian (SAS) AF: 0.150 AC: 723 AN: 4828

European-Finnish (FIN) AF: 0.267 AC: 2828 AN: 10602

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10581 AN: 68004

Other (OTH) AF: 0.174 AC: 368 AN: 2110

Alfa AF: 0.104 Hom.: 211

Bravo AF: 0.172

Asia WGS AF: 0.171 AC: 595 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.3
DANN	Benign	0.80
PhyloP100		-0.026
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs334892; hg19: chr5-54528393; COSMIC: COSV57004576; COSMIC: COSV57004576;