Variant chr15-59114468-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004701.4(CCNB2):c.292G>A(p.Val98Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,457,580 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: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CCNB2
NM_004701.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.575

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]

CCNB2 links:

CCNB2 (HGNC:):

CCNB2 links:

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=0.04449013).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNB2	NM_004701.4 linkuse as main transcript	c.292G>A	p.Val98Ile	missense_variant	4/9	ENST00000288207.7	NP_004692.1	O95067

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCNB2	ENST00000288207.7 linkuse as main transcript	c.292G>A	p.Val98Ile	missense_variant	4/9	1	NM_004701.4	ENSP00000288207.2	O95067
CCNB2	ENST00000621385.1 linkuse as main transcript	c.292G>A	p.Val98Ile	missense_variant	4/8	1		ENSP00000480809.1	H1UBN3
CCNB2	ENST00000559622.5 linkuse as main transcript	c.49G>A	p.Val17Ile	missense_variant	2/6	5		ENSP00000453685.1	H0YMP3
CCNB2	ENST00000561077.1 linkuse as main transcript	n.541G>A		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

247744

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

133940

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:

0.000101

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1457580

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724920

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:

0.0000234

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 08, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.9

DANN

Benign

0.92

DEOGEN2

Benign

0.077

T;T;.

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.40

T;T;T

M_CAP

Benign

0.0088

MetaRNN

Benign

0.044

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;.;.

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.51

N;N;.

REVEL

Benign

0.063

Sift

Benign

0.44

T;T;.

Sift4G

Benign

0.52

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.051

MutPred

0.15

Gain of helix (P = 0.0854);.;Gain of helix (P = 0.0854);

MVP

0.32

MPC

0.088

ClinPred

0.028

GERP RS

1.1

Varity_R

0.013

gMVP

0.17

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over