chr15-59107431-G-T

Variant names:

• chr15-59107431-G-T
• NM_004701.4:c.134G>T

Variant summary

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

The NM_004701.4(CCNB2):​c.134G>T​(p.Arg45Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,776 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 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: 0.0000048 (0 hom.)
• Consequence: CCNB2 NM_004701.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.30

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]

ACMG classification

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 rank	MANE	Protein	UniProt
CCNB2	NM_004701.4	c.134G>T	p.Arg45Ile	missense_variant	Exon 2 of 9	ENST00000288207.7	NP_004692.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNB2	ENST00000288207.7	c.134G>T	p.Arg45Ile	missense_variant	Exon 2 of 9	1	NM_004701.4	ENSP00000288207.2
CCNB2	ENST00000621385.1	c.134G>T	p.Arg45Ile	missense_variant	Exon 2 of 8	1		ENSP00000480809.1
CCNB2	ENST00000559622.5	c.24+2139G>T		intron_variant	Intron 1 of 5	5		ENSP00000453685.1
CCNB2	ENST00000561077.1	n.277G>T		non_coding_transcript_exon_variant	Exon 2 of 3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461776 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4 AN XY: 727184

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.16	T;.
Eigen	Benign	0.030
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.1	N;.
REVEL	Benign	0.14
Sift	Benign	0.096	T;.
Sift4G	Benign	0.11	T;T
Polyphen		0.29	B;.
Vest4		0.53
MutPred		0.47		Loss of solvent accessibility (P = 0.0159);Loss of solvent accessibility (P = 0.0159);
MVP		0.76
MPC		0.32
ClinPred		0.51	D
GERP RS		3.8
Varity_R		0.073
gMVP		0.34

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-59399630;