20-3800783-C-T

Variant summary

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

The NM_021873.4(CDC25B):​c.500C>T​(p.Thr167Ile) 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

Scores

10
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.82
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
CDC25BNM_021873.4 linkc.500C>T p.Thr167Ile missense_variant Exon 6 of 16 ENST00000245960.10 NP_068659.1 P30305-1B3KS38Q6MZW8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDC25BENST00000245960.10 linkc.500C>T p.Thr167Ile missense_variant Exon 6 of 16 1 NM_021873.4 ENSP00000245960.5 P30305-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 10, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.500C>T (p.T167I) alteration is located in exon 6 (coding exon 6) of the CDC25B gene. This alteration results from a C to T substitution at nucleotide position 500, causing the threonine (T) at amino acid position 167 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.42
BayesDel_addAF
Uncertain
0.069
T
BayesDel_noAF
Benign
-0.14
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.015
T;.;T;.
Eigen
Uncertain
0.51
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Uncertain
0.91
D;D;D;D
M_CAP
Benign
0.023
T
MetaRNN
Uncertain
0.58
D;D;D;D
MetaSVM
Benign
-0.87
T
MutationAssessor
Uncertain
2.8
.;.;M;.
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-1.7
N;N;N;N
REVEL
Benign
0.15
Sift
Benign
0.22
T;T;T;T
Sift4G
Benign
0.32
T;T;T;T
Polyphen
1.0, 1.0, 1.0
.;D;D;D
Vest4
0.58
MutPred
0.51
.;.;Loss of solvent accessibility (P = 0.0769);.;
MVP
0.45
MPC
0.91
ClinPred
0.99
D
GERP RS
4.8
Varity_R
0.082
gMVP
0.33

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: chr20-3781430; API