rs768589001

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004701.4(CCNB2):​c.53C>A​(p.Thr18Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000679 in 147,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CCNB2
NM_004701.4 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.521
Variant links:
Genes affected
CCNB2 (HGNC:1580): (cyclin B2) Cyclin B2 is a member of the cyclin family, specifically the B-type cyclins. The B-type cyclins, B1 and B2, associate with p34cdc2 and are essential components of the cell cycle regulatory machinery. B1 and B2 differ in their subcellular localization. Cyclin B1 co-localizes with microtubules, whereas cyclin B2 is primarily associated with the Golgi region. Cyclin B2 also binds to transforming growth factor beta RII and thus cyclin B2/cdc2 may play a key role in transforming growth factor beta-mediated cell cycle control. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06307292).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCNB2NM_004701.4 linkc.53C>A p.Thr18Lys missense_variant Exon 2 of 9 ENST00000288207.7 NP_004692.1 O95067

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCNB2ENST00000288207.7 linkc.53C>A p.Thr18Lys missense_variant Exon 2 of 9 1 NM_004701.4 ENSP00000288207.2 O95067
CCNB2ENST00000621385.1 linkc.53C>A p.Thr18Lys missense_variant Exon 2 of 8 1 ENSP00000480809.1 H1UBN3
CCNB2ENST00000559622.5 linkc.24+2058C>A intron_variant Intron 1 of 5 5 ENSP00000453685.1 H0YMP3
CCNB2ENST00000561077.1 linkn.196C>A non_coding_transcript_exon_variant Exon 2 of 3 5

Frequencies

GnomAD3 genomes
AF:
0.00000679
AC:
1
AN:
147214
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000148
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1453456
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
723160
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000679
AC:
1
AN:
147214
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
71250
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000148
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.071
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.78
CADD
Benign
1.9
DANN
Benign
0.19
DEOGEN2
Benign
0.045
T;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.41
T;T
M_CAP
Benign
0.0060
T
MetaRNN
Benign
0.063
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.49
N;.
PrimateAI
Benign
0.36
T
PROVEAN
Benign
0.23
N;.
REVEL
Benign
0.029
Sift
Benign
0.83
T;.
Sift4G
Benign
0.94
T;T
Polyphen
0.0
B;.
Vest4
0.18
MutPred
0.40
Gain of ubiquitination at T18 (P = 0.0177);Gain of ubiquitination at T18 (P = 0.0177);
MVP
0.27
MPC
0.13
ClinPred
0.055
T
GERP RS
0.017
Varity_R
0.020
gMVP
0.29

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs768589001; hg19: chr15-59399549; API