5-55232560-G-C

Variant names:

• chr5-55232560-G-C
• rs72749883
• NM_021147.5:c.382-14C>G

Variant summary

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

The NM_021147.5(CCNO):​c.382-14C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0799 in 1,612,396 control chromosomes in the GnomAD database, including 5,723 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.065 (389 hom., cov: 33)
  • Exomes 𝑓: 0.082 (5334 hom.)
• Consequence: CCNO NM_021147.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.780
• Publications: 6 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: Labcorp Genetics (formerly Invitae), G2P, 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=-0.69).
• BP6: Variant 5-55232560-G-C is Benign according to our data. Variant chr5-55232560-G-C is described in ClinVar as Benign. ClinVar VariationId is 402509.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0849 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021147.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNO	NM_021147.5	MANE Select	c.382-14C>G		intron	N/A	NP_066970.3	P22674-1
	CCNO	NR_125348.1		n.432C>G		non_coding_transcript_exon	Exon 1 of 2
	CCNO	NR_125346.2		n.843-14C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNO	ENST00000282572.5	TSL:1 MANE Select	c.382-14C>G		intron	N/A	ENSP00000282572.4	P22674-1
	CCNO	ENST00000501463.2	TSL:1	n.*362-14C>G		intron	N/A	ENSP00000422485.1	P22674-2

Frequencies

GnomAD3 genomes AF: 0.0647 AC: 9852 AN: 152216 Hom.: 389 Cov.: 33

Gnomad AFR AF: 0.0325

Gnomad AMI AF: 0.0945

Gnomad AMR AF: 0.0659

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0532

Gnomad FIN AF: 0.0651

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0868

Gnomad OTH AF: 0.0794

GnomAD2 exomes AF: 0.0645 AC: 15861 AN: 246032 AF XY: 0.0664

Gnomad AFR exome AF: 0.0324

Gnomad AMR exome AF: 0.0457

Gnomad ASJ exome AF: 0.0985

Gnomad EAS exome AF: 0.000381

Gnomad FIN exome AF: 0.0598

Gnomad NFE exome AF: 0.0854

Gnomad OTH exome AF: 0.0781

GnomAD4 exome AF: 0.0815 AC: 119039 AN: 1460062 Hom.: 5334 Cov.: 32 AF XY: 0.0809 AC XY: 58749 AN XY: 726332

African (AFR) AF: 0.0300 AC: 1004 AN: 33464

American (AMR) AF: 0.0479 AC: 2140 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0980 AC: 2559 AN: 26116

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39690

South Asian (SAS) AF: 0.0560 AC: 4831 AN: 86212

European-Finnish (FIN) AF: 0.0574 AC: 3022 AN: 52638

Middle Eastern (MID) AF: 0.0970 AC: 551 AN: 5678

European-Non Finnish (NFE) AF: 0.0899 AC: 99848 AN: 1111232

Other (OTH) AF: 0.0841 AC: 5075 AN: 60330

GnomAD4 genome AF: 0.0647 AC: 9853 AN: 152334 Hom.: 389 Cov.: 33 AF XY: 0.0637 AC XY: 4741 AN XY: 74480

African (AFR) AF: 0.0326 AC: 1354 AN: 41582

American (AMR) AF: 0.0658 AC: 1007 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 359 AN: 3468

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5182

South Asian (SAS) AF: 0.0528 AC: 255 AN: 4828

European-Finnish (FIN) AF: 0.0651 AC: 691 AN: 10618

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0868 AC: 5905 AN: 68032

Other (OTH) AF: 0.0781 AC: 165 AN: 2112

Alfa AF: 0.0466 Hom.: 60

Bravo AF: 0.0638

Asia WGS AF: 0.0250 AC: 86 AN: 3478

ClinVar

ClinVar submissions

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	-0.69
CADD	Benign	12
DANN	Benign	0.86
PhyloP100		0.78
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs72749883; hg19: chr5-54528388;