chr20-3800773-C-G

Variant names:

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

Variant summary

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

The NM_021873.4(CDC25B):​c.490C>G​(p.Arg164Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R164W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CDC25B NM_021873.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.618
• Publications: 2 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.490C>G	p.Arg164Gly	missense	Exon 6 of 16	NP_068659.1	P30305-1
	CDC25B	NM_004358.5		c.448C>G	p.Arg150Gly	missense	Exon 6 of 16	NP_004349.1	P30305-2
	CDC25B	NM_001287516.2		c.298C>G	p.Arg100Gly	missense	Exon 6 of 16	NP_001274445.1	B4DIG0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC25B	ENST00000245960.10	TSL:1 MANE Select	c.490C>G	p.Arg164Gly	missense	Exon 6 of 16	ENSP00000245960.5	P30305-1
	CDC25B	ENST00000439880.6	TSL:1	c.448C>G	p.Arg150Gly	missense	Exon 6 of 16	ENSP00000405972.2	P30305-2
	CDC25B	ENST00000340833.4	TSL:1	c.460-198C>G		intron	N/A	ENSP00000339170.4	P30305-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459016 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726018

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111990

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.087
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.62
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.11
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.88	P
Vest4		0.50
MutPred		0.69		Loss of MoRF binding (P = 0.0154)
MVP		0.25
MPC		0.39
ClinPred		0.96	D
GERP RS		2.7
Varity_R		0.20
gMVP		0.42
Mutation Taster		=77/23	polymorphism

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

Other links and lift over

dbSNP: rs371350767; hg19: chr20-3781420;