dbSNP rs138440180: CCNO:p.Gly264Trp (chr5-55231638-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021147.5(CCNO):c.790G>T(p.Gly264Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,446,736 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G264R) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CCNO
NM_021147.5 missense

Scores

Clinical Significance

Not reported in ClinVar

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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
CCNO	NM_021147.5 link	c.790G>T	p.Gly264Trp	missense_variant	Exon 3 of 3	ENST00000282572.5	NP_066970.3
CCNO	NR_125346.2 link	n.1251G>T		non_coding_transcript_exon_variant	Exon 3 of 3
CCNO	NR_125347.2 link	n.880G>T		non_coding_transcript_exon_variant	Exon 3 of 3
CCNO	NR_125348.1 link	n.854G>T		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>T	p.Gly264Trp	missense_variant	Exon 3 of 3	1	NM_021147.5	ENSP00000282572.4
CCNO	ENST00000501463.2 link	n.*770G>T		non_coding_transcript_exon_variant	Exon 3 of 3	1		ENSP00000422485.1
CCNO	ENST00000501463.2 link	n.*770G>T		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000422485.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000462

AC:

AN:

216294

AF XY:

0.00000848

show subpopulations

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000106

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1446736

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

718758

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33174

American (AMR)

AF:

0.00

AC:

AN:

42084

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25792

East Asian (EAS)

AF:

0.00

AC:

AN:

38882

South Asian (SAS)

AF:

0.00

AC:

AN:

84744

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51214

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1105332

Other (OTH)

AF:

0.00

AC:

AN:

59774

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000829

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

Eigen

Benign

0.029

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.79

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.59

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.6

PhyloP100

4.1

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-2.0

REVEL

Benign

0.25

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.52

MutPred

0.63

Loss of disorder (P = 0.0396);

MVP

0.69

MPC

1.4

ClinPred

0.84

GERP RS

4.4

Varity_R

0.49

gMVP

0.64

Mutation Taster

=92/8

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over