5-55231638-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_021147.5(CCNO):c.790G>C(p.Gly264Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00124 in 1,599,092 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0066 ( 14 hom., cov: 33)

Exomes 𝑓: 0.00068 ( 7 hom. )

Consequence

CCNO
NM_021147.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.12

Publications

1 publications found

Variant links:

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

CCNO links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.009183466).

BP6

Variant 5-55231638-C-G is Benign according to our data. Variant chr5-55231638-C-G is described in ClinVar as Benign. ClinVar VariationId is 416793.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00656 (1000/152358) while in subpopulation AFR AF = 0.0228 (950/41584). AF 95% confidence interval is 0.0216. There are 14 homozygotes in GnomAd4. There are 441 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 14 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
CCNO	NM_021147.5 link	c.790G>C	p.Gly264Arg	missense_variant	Exon 3 of 3	ENST00000282572.5	NP_066970.3
CCNO	NR_125346.2 link	n.1251G>C		non_coding_transcript_exon_variant	Exon 3 of 3
CCNO	NR_125347.2 link	n.880G>C		non_coding_transcript_exon_variant	Exon 3 of 3
CCNO	NR_125348.1 link	n.854G>C		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
CCNO	ENST00000282572.5 link	c.790G>C	p.Gly264Arg	missense_variant	Exon 3 of 3	1	NM_021147.5	ENSP00000282572.4
CCNO	ENST00000501463.2 link	n.*770G>C		non_coding_transcript_exon_variant	Exon 3 of 3	1		ENSP00000422485.1
CCNO	ENST00000501463.2 link	n.*770G>C		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000422485.1

Frequencies

GnomAD3 genomes

AF:

0.00653

AC:

994

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0228

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00334

GnomAD2 exomes

AF:

0.00166

AC:

358

AN:

216294

AF XY:

0.00105

show subpopulations

Gnomad AFR exome

AF:

0.0244

Gnomad AMR exome

AF:

0.000875

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000849

Gnomad OTH exome

AF:

0.000737

GnomAD4 exome

AF:

0.000675

AC:

977

AN:

1446734

Hom.:

Cov.:

AF XY:

0.000558

AC XY:

401

AN XY:

718758

show subpopulations

African (AFR)

AF:

0.0230

AC:

762

AN:

33172

American (AMR)

AF:

0.00114

AC:

AN:

42084

Ashkenazi Jewish (ASJ)

AF:

0.0000388

AC:

AN:

25792

East Asian (EAS)

AF:

0.00

AC:

AN:

38882

South Asian (SAS)

AF:

0.0000472

AC:

AN:

84744

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51214

Middle Eastern (MID)

AF:

0.00174

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.0000389

AC:

AN:

1105332

Other (OTH)

AF:

0.00182

AC:

109

AN:

59774

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

128

191

255

319

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00656

AC:

1000

AN:

152358

Hom.:

Cov.:

AF XY:

0.00592

AC XY:

441

AN XY:

74518

show subpopulations

African (AFR)

AF:

0.0228

AC:

950

AN:

41584

American (AMR)

AF:

0.00229

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68030

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

141

188

235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00190

Hom.:

Bravo

AF:

0.00752

ESP6500AA

AF:

0.0221

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00186

AC:

225

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

Eigen

Benign

0.025

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.77

MetaRNN

Benign

0.0092

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.3

PhyloP100

4.1

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.15

Sift

Uncertain

0.024

Sift4G

Uncertain

0.017

Polyphen

1.0

Vest4

0.30

MutPred

0.62

Gain of loop (P = 0.1069);

MVP

0.69

MPC

0.97

ClinPred

0.020

GERP RS

4.4

Varity_R

0.52

gMVP

0.58

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over