Variant chr15-59107670-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_004701.4(CCNB2):c.267G>A(p.Lys89=) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.00903 in 1,611,998 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0062 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0093 ( 78 hom. )

Consequence

CCNB2
NM_004701.4 splice_region, synonymous

Scores

Splicing: ADA: 0.9996

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.69

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]

CCNB2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6

Variant 15-59107670-G-A is Benign according to our data. Variant chr15-59107670-G-A is described in ClinVar as [Benign]. Clinvar id is 777248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCNB2	NM_004701.4 linkuse as main transcript	c.267G>A	p.Lys89=	splice_region_variant, synonymous_variant	3/9	ENST00000288207.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CCNB2	ENST00000288207.7 linkuse as main transcript	c.267G>A	p.Lys89=	splice_region_variant, synonymous_variant	3/9	1	NM_004701.4	P1
CCNB2	ENST00000621385.1 linkuse as main transcript	c.267G>A	p.Lys89=	splice_region_variant, synonymous_variant	3/8	1
CCNB2	ENST00000559622.5 linkuse as main transcript	c.24+2378G>A		intron_variant		5
CCNB2	ENST00000561077.1 linkuse as main transcript	n.516G>A		splice_region_variant, non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes

AF:

0.00618

AC:

941

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00191

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00236

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0110

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00572

AC:

1430

AN:

250176

Hom.:

AF XY:

0.00580

AC XY:

784

AN XY:

135286

show subpopulations

Gnomad AFR exome

AF:

0.00136

Gnomad AMR exome

AF:

0.00178

Gnomad ASJ exome

AF:

0.000697

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000493

Gnomad FIN exome

AF:

0.00361

Gnomad NFE exome

AF:

0.0107

Gnomad OTH exome

AF:

0.00508

GnomAD4 exome

AF:

0.00933

AC:

13612

AN:

1459696

Hom.:

Cov.:

AF XY:

0.00919

AC XY:

6676

AN XY:

726236

show subpopulations

Gnomad4 AFR exome

AF:

0.00147

Gnomad4 AMR exome

AF:

0.00209

Gnomad4 ASJ exome

AF:

0.000421

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000546

Gnomad4 FIN exome

AF:

0.00364

Gnomad4 NFE exome

AF:

0.0115

Gnomad4 OTH exome

AF:

0.00720

GnomAD4 genome

AF:

0.00619

AC:

942

AN:

152302

Hom.:

Cov.:

AF XY:

0.00555

AC XY:

413

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00190

Gnomad4 AMR

AF:

0.00470

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00236

Gnomad4 NFE

AF:

0.0110

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.0100

Hom.:

Bravo

AF:

0.00659

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00851

EpiControl

AF:

0.00854

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.97

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.24

Position offset: 36

DS_DL_spliceai

0.21

Position offset: 0

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