20-3800773-C-T

Variant names:

• chr20-3800773-C-T
• rs371350767
• NM_021873.4:c.490C>T

Variant summary

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

The NM_021873.4(CDC25B):​c.490C>T​(p.Arg164Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,459,016 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: CDC25B NM_021873.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.618

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

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
CDC25B	NM_021873.4	c.490C>T	p.Arg164Trp	missense_variant	Exon 6 of 16	ENST00000245960.10	NP_068659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC25B	ENST00000245960.10	c.490C>T	p.Arg164Trp	missense_variant	Exon 6 of 16	1	NM_021873.4	ENSP00000245960.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000121 AC: 3 AN: 247198 Hom.: 0 AF XY: 0.0000223 AC XY: 3 AN XY: 134494

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1459016 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 726018

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000659 Hom.: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.490C>T (p.R164W) 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 490, causing the arginine (R) at amino acid position 164 to be replaced by a tryptophan (W). 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	Benign	0.15
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.034	T;.;T;.
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.58	D;D;D;D
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.6	.;.;M;.
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.7	D;D;D;D
REVEL	Benign	0.21
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		1.0, 1.0	.;D;D;D
Vest4		0.52
MVP		0.39
MPC		0.91
ClinPred		0.91	D
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs371350767; hg19: chr20-3781420;