chr15-59107670-G-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_004701.4(CCNB2):​c.267G>A​(p.Lys89Lys) 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

2
Splicing: ADA: 0.9996
2

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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank MANE Protein UniProt
CCNB2NM_004701.4 linkc.267G>A p.Lys89Lys splice_region_variant, synonymous_variant Exon 3 of 9 ENST00000288207.7 NP_004692.1 O95067

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCNB2ENST00000288207.7 linkc.267G>A p.Lys89Lys splice_region_variant, synonymous_variant Exon 3 of 9 1 NM_004701.4 ENSP00000288207.2 O95067
CCNB2ENST00000621385.1 linkc.267G>A p.Lys89Lys splice_region_variant, synonymous_variant Exon 3 of 8 1 ENSP00000480809.1 H1UBN3
CCNB2ENST00000559622.5 linkc.24+2378G>A intron_variant Intron 1 of 5 5 ENSP00000453685.1 H0YMP3
CCNB2ENST00000561077.1 linkn.516G>A splice_region_variant, non_coding_transcript_exon_variant Exon 2 of 3 5

Frequencies

GnomAD3 genomes
AF:
0.00618
AC:
941
AN:
152184
Hom.:
4
Cov.:
32
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
GnomAD2 exomes
AF:
0.00572
AC:
1430
AN:
250176
AF XY:
0.00580
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 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.:
78
Cov.:
32
AF XY:
0.00919
AC XY:
6676
AN XY:
726236
show subpopulations
Gnomad4 AFR exome
AF:
0.00147
AC:
49
AN:
33386
Gnomad4 AMR exome
AF:
0.00209
AC:
93
AN:
44480
Gnomad4 ASJ exome
AF:
0.000421
AC:
11
AN:
26104
Gnomad4 EAS exome
AF:
0.00
AC:
0
AN:
39690
Gnomad4 SAS exome
AF:
0.000546
AC:
47
AN:
86104
Gnomad4 FIN exome
AF:
0.00364
AC:
194
AN:
53314
Gnomad4 NFE exome
AF:
0.0115
AC:
12779
AN:
1110542
Gnomad4 Remaining exome
AF:
0.00720
AC:
434
AN:
60314
Heterozygous variant carriers
0
678
1357
2035
2714
3392
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
472
944
1416
1888
2360
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.00619
AC:
942
AN:
152302
Hom.:
4
Cov.:
32
AF XY:
0.00555
AC XY:
413
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.00190
AC:
0.00190087
AN:
0.00190087
Gnomad4 AMR
AF:
0.00470
AC:
0.00470404
AN:
0.00470404
Gnomad4 ASJ
AF:
0.000577
AC:
0.000576701
AN:
0.000576701
Gnomad4 EAS
AF:
0.00
AC:
0
AN:
0
Gnomad4 SAS
AF:
0.000829
AC:
0.000829187
AN:
0.000829187
Gnomad4 FIN
AF:
0.00236
AC:
0.00235538
AN:
0.00235538
Gnomad4 NFE
AF:
0.0110
AC:
0.0110115
AN:
0.0110115
Gnomad4 OTH
AF:
0.00520
AC:
0.00520341
AN:
0.00520341
Heterozygous variant carriers
0
48
96
144
192
240
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
20
40
60
80
100
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00915
Hom.:
11
Bravo
AF:
0.00659
Asia WGS
AF:
0.000289
AC:
1
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
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Jun 26, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.21
CADD
Benign
22
DANN
Benign
0.88
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Mutation Taster
=14/86
disease causing

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.

Other links and lift over

dbSNP: rs35033821; hg19: chr15-59399869; API