Genetic Variant CDC25B:p.Pro153Ser (chr20-3800496-C-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_021873.4(CDC25B):c.457C>T(p.Pro153Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P153T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

CDC25B
NM_021873.4 missense, splice_region

Scores

Splicing: ADA: 0.9917

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.22

Publications

0 publications found

Variant links:

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]

CDC25B links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.906

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDC25B	NM_021873.4	MANE Select	c.457C>T	p.Pro153Ser	missense splice_region	Exon 5 of 16	NP_068659.1	P30305-1
CDC25B	NM_004358.5		c.415C>T	p.Pro139Ser	missense splice_region	Exon 5 of 16	NP_004349.1	P30305-2
CDC25B	NM_021872.4		c.457C>T	p.Pro153Ser	missense splice_region	Exon 5 of 15	NP_068658.1	P30305-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDC25B	ENST00000245960.10	TSL:1 MANE Select	c.457C>T	p.Pro153Ser	missense splice_region	Exon 5 of 16	ENSP00000245960.5	P30305-1
CDC25B	ENST00000439880.6	TSL:1	c.415C>T	p.Pro139Ser	missense splice_region	Exon 5 of 16	ENSP00000405972.2	P30305-2
CDC25B	ENST00000340833.4	TSL:1	c.457C>T	p.Pro153Ser	missense splice_region	Exon 5 of 15	ENSP00000339170.4	P30305-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.094

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.75

M_CAP

Benign

0.026

MetaRNN

Pathogenic

0.91

MetaSVM

Benign

-0.79

MutationAssessor

Pathogenic

3.4

PhyloP100

3.2

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-5.6

REVEL

Uncertain

0.47

Sift

Uncertain

0.0080

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.67

MutPred

0.81

Gain of MoRF binding (P = 0.0731)

MVP

0.63

MPC

0.89

ClinPred

1.0

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.36

gMVP

0.74

Mutation Taster

=84/16

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Benign

0.68

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over