chr15-59116746-G-C
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004701.4(CCNB2):āc.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
NM_004701.4 missense
Scores
5
8
6
Clinical Significance
Conservation
PhyloP100: 1.69
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]
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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 |
---|---|---|---|---|---|---|---|
CCNB2 | NM_004701.4 | c.654G>C | p.Leu218Phe | missense_variant | 6/9 | ENST00000288207.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCNB2 | ENST00000288207.7 | c.654G>C | p.Leu218Phe | missense_variant | 6/9 | 1 | NM_004701.4 | P1 | |
CCNB2 | ENST00000621385.1 | c.654G>C | p.Leu218Phe | missense_variant | 6/8 | 1 | |||
CCNB2 | ENST00000559622.5 | c.411G>C | p.Leu137Phe | missense_variant | 4/6 | 5 | |||
CCNB2 | ENST00000559301.1 | upstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152154Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1460912Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 726760
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152154Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74334
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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 submitter | clinical testing | Ambry Genetics | Nov 18, 2021 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;N;.
REVEL
Uncertain
Sift
Uncertain
D;D;.
Sift4G
Uncertain
D;D;D
Polyphen
D;.;.
Vest4
MutPred
Loss of helix (P = 0.1299);.;Loss of helix (P = 0.1299);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at