20-3801001-C-T

Variant names:

• chr20-3801001-C-T
• rs2089261696
• NM_021873.4:c.613C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021873.4(CDC25B):​c.613C>T​(p.Pro205Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDC25B NM_021873.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.32
• Publications: 0 publications found

Genes affected

CDC25B (HGNC:1726): (cell division cycle 25B) CDC25B is a member of the CDC25 family of phosphatases. CDC25B activates the cyclin dependent kinase CDC2 by removing two phosphate groups and it is required for entry into mitosis. CDC25B shuttles between the nucleus and the cytoplasm due to nuclear localization and nuclear export signals. The protein is nuclear in the M and G1 phases of the cell cycle and moves to the cytoplasm during S and G2. CDC25B has oncogenic properties, although its role in tumor formation has not been determined. Multiple transcript variants for this gene exist. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021873.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC25B	NM_021873.4	MANE Select	c.613C>T	p.Pro205Ser	missense	Exon 7 of 16	NP_068659.1	P30305-1
	CDC25B	NM_004358.5		c.571C>T	p.Pro191Ser	missense	Exon 7 of 16	NP_004349.1	P30305-2
	CDC25B	NM_021872.4		c.490C>T	p.Pro164Ser	missense	Exon 6 of 15	NP_068658.1	P30305-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC25B	ENST00000245960.10	TSL:1 MANE Select	c.613C>T	p.Pro205Ser	missense	Exon 7 of 16	ENSP00000245960.5	P30305-1
	CDC25B	ENST00000439880.6	TSL:1	c.571C>T	p.Pro191Ser	missense	Exon 7 of 16	ENSP00000405972.2	P30305-2
	CDC25B	ENST00000340833.4	TSL:1	c.490C>T	p.Pro164Ser	missense	Exon 6 of 15	ENSP00000339170.4	P30305-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.3
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.17
Sift	Benign	0.037	D
Sift4G	Uncertain	0.019	D
Polyphen		0.28	B
Vest4		0.21
MutPred		0.73		Gain of phosphorylation at P205 (P = 0.0542)
MVP		0.39
MPC		0.32
ClinPred		0.93	D
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.45
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

dbSNP: rs2089261696; hg19: chr20-3781648;