chr15-59116746-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004701.4(CCNB2):ā€‹c.654G>Cā€‹(p.Leu218Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,066 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.000014 ( 0 hom. )

Consequence

CCNB2
NM_004701.4 missense

Scores

5
8
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.69
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CCNB2NM_004701.4 linkuse as main transcriptc.654G>C p.Leu218Phe missense_variant 6/9 ENST00000288207.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CCNB2ENST00000288207.7 linkuse as main transcriptc.654G>C p.Leu218Phe missense_variant 6/91 NM_004701.4 P1
CCNB2ENST00000621385.1 linkuse as main transcriptc.654G>C p.Leu218Phe missense_variant 6/81
CCNB2ENST00000559622.5 linkuse as main transcriptc.411G>C p.Leu137Phe missense_variant 4/65
CCNB2ENST00000559301.1 linkuse as main transcript upstream_gene_variant 2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152154
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:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000137
AC:
20
AN:
1460912
Hom.:
0
Cov.:
32
AF XY:
0.0000138
AC XY:
10
AN XY:
726760
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.0000162
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152154
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.00000756
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 18, 2021The c.654G>C (p.L218F) alteration is located in exon 6 (coding exon 6) of the CCNB2 gene. This alteration results from a G to C substitution at nucleotide position 654, causing the leucine (L) at amino acid position 218 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.71
BayesDel_addAF
Benign
-0.035
T
BayesDel_noAF
Benign
-0.29
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.34
T;T;.
Eigen
Pathogenic
0.76
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Uncertain
0.96
D;D;D
M_CAP
Benign
0.019
T
MetaRNN
Uncertain
0.68
D;D;D
MetaSVM
Benign
-0.82
T
MutationAssessor
Pathogenic
3.5
M;.;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.71
T
PROVEAN
Uncertain
-2.4
N;N;.
REVEL
Uncertain
0.37
Sift
Uncertain
0.0020
D;D;.
Sift4G
Uncertain
0.0020
D;D;D
Polyphen
0.96
D;.;.
Vest4
0.55
MutPred
0.70
Loss of helix (P = 0.1299);.;Loss of helix (P = 0.1299);
MVP
0.80
MPC
0.54
ClinPred
0.94
D
GERP RS
4.3
Varity_R
0.64
gMVP
0.69

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs1434276500; hg19: chr15-59408945; API