15-59114740-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004701.4(CCNB2):​c.461A>T​(p.His154Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,612,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CCNB2
NM_004701.4 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.569
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31444773).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCNB2NM_004701.4 linkc.461A>T p.His154Leu missense_variant Exon 5 of 9 ENST00000288207.7 NP_004692.1 O95067

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCNB2ENST00000288207.7 linkc.461A>T p.His154Leu missense_variant Exon 5 of 9 1 NM_004701.4 ENSP00000288207.2 O95067
CCNB2ENST00000621385.1 linkc.461A>T p.His154Leu missense_variant Exon 5 of 8 1 ENSP00000480809.1 H1UBN3
CCNB2ENST00000559622.5 linkc.218A>T p.His73Leu missense_variant Exon 3 of 6 5 ENSP00000453685.1 H0YMP3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152186
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251006
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135674
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1460110
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726018
show subpopulations
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:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152186
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74338
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.094
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
9.0
DANN
Benign
0.93
DEOGEN2
Benign
0.18
T;T;.
Eigen
Benign
-0.69
Eigen_PC
Benign
-0.63
FATHMM_MKL
Benign
0.42
N
LIST_S2
Benign
0.62
T;T;T
M_CAP
Benign
0.0059
T
MetaRNN
Benign
0.31
T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.3
L;.;.
PrimateAI
Benign
0.32
T
PROVEAN
Uncertain
-2.9
D;D;.
REVEL
Benign
0.054
Sift
Benign
0.13
T;T;.
Sift4G
Benign
0.23
T;T;T
Polyphen
0.0
B;.;.
Vest4
0.60
MutPred
0.50
Loss of disorder (P = 0.0763);.;Loss of disorder (P = 0.0763);
MVP
0.57
MPC
0.18
ClinPred
0.13
T
GERP RS
0.81
Varity_R
0.20
gMVP
0.47

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs779036918; hg19: chr15-59406939; API