NM_004701.4:c.613C>G

Variant names:

• chr15-59116705-C-G
• NM_004701.4:c.613C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_004701.4(CCNB2):​c.613C>G​(p.Arg205Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 6.9e-7 (0 hom.)
• Consequence: CCNB2 NM_004701.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.843

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNB2	NM_004701.4	c.613C>G	p.Arg205Gly	missense_variant	Exon 6 of 9	ENST00000288207.7	NP_004692.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNB2	ENST00000288207.7	c.613C>G	p.Arg205Gly	missense_variant	Exon 6 of 9	1	NM_004701.4	ENSP00000288207.2
CCNB2	ENST00000621385.1	c.613C>G	p.Arg205Gly	missense_variant	Exon 6 of 8	1		ENSP00000480809.1
CCNB2	ENST00000559622.5	c.370C>G	p.Arg124Gly	missense_variant	Exon 4 of 6	5		ENSP00000453685.1
CCNB2	ENST00000559301.1	n.-62C>G		upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457748 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724896

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: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T;T;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.71	T;T;T
M_CAP	Uncertain	0.086	D
MetaRNN	Pathogenic	0.84	D;D;D
MetaSVM	Benign	-0.71	T
MutationAssessor	Pathogenic	3.7	H;.;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-5.5	D;D;.
REVEL	Uncertain	0.39
Sift	Uncertain	0.0010	D;D;.
Sift4G	Uncertain	0.016	D;D;D
Polyphen		0.77	P;.;.
Vest4		0.80
MutPred		0.68		Loss of stability (P = 0.0405);.;Loss of stability (P = 0.0405);
MVP		0.81
MPC		0.59
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.87
gMVP		0.64

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: chr15-59408904;