chr20-3798445-C-A

Variant names:

• chr20-3798445-C-A
• rs2089146482
• NM_021873.4:c.362C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_021873.4(CDC25B):​c.362C>A​(p.Pro121His) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,446,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CDC25B NM_021873.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.99
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30268627).

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.362C>A	p.Pro121His	missense	Exon 3 of 16	NP_068659.1	P30305-1
	CDC25B	NM_004358.5		c.320C>A	p.Pro107His	missense	Exon 3 of 16	NP_004349.1	P30305-2
	CDC25B	NM_021872.4		c.362C>A	p.Pro121His	missense	Exon 3 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.362C>A	p.Pro121His	missense	Exon 3 of 16	ENSP00000245960.5	P30305-1
	CDC25B	ENST00000439880.6	TSL:1	c.320C>A	p.Pro107His	missense	Exon 3 of 16	ENSP00000405972.2	P30305-2
	CDC25B	ENST00000340833.4	TSL:1	c.362C>A	p.Pro121His	missense	Exon 3 of 15	ENSP00000339170.4	P30305-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446848 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 719328

African (AFR) AF: 0.0000304 AC: 1 AN: 32866

American (AMR) AF: 0.00 AC: 0 AN: 42750

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25898

East Asian (EAS) AF: 0.00 AC: 0 AN: 38552

South Asian (SAS) AF: 0.00 AC: 0 AN: 83636

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53236

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104394

Other (OTH) AF: 0.00 AC: 0 AN: 59780

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

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	0.11
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.030	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		4.0
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.11
Sift	Benign	0.088	T
Sift4G	Benign	0.58	T
Polyphen		1.0	D
Vest4		0.54
MutPred		0.29		Loss of glycosylation at P121 (P = 0.089)
MVP		0.33
MPC		0.96
ClinPred		0.97	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.072
gMVP		0.38
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2089146482; hg19: chr20-3779092;