NM_001789.3:c.470G>C

Variant names:

• chr3-48180800-C-G
• rs372655408
• NM_001789.3:c.470G>C

Variant summary

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

The NM_001789.3(CDC25A):​c.470G>C​(p.Arg157Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R157H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CDC25A NM_001789.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.54
• Publications: 0 publications found

Genes affected

CDC25A (HGNC:1725): (cell division cycle 25A) CDC25A is a member of the CDC25 family of phosphatases. CDC25A is required for progression from G1 to the S phase of the cell cycle. It activates the cyclin-dependent kinase CDC2 by removing two phosphate groups. CDC25A is specifically degraded in response to DNA damage, which prevents cells with chromosomal abnormalities from progressing through cell division. CDC25A is an oncogene, although its exact role in oncogenesis has not been demonstrated. Two transcript variants encoding different isoforms have been found for this gene. [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_001789.3. 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
	CDC25A	NM_001789.3	MANE Select	c.470G>C	p.Arg157Pro	missense	Exon 6 of 15	NP_001780.2
	CDC25A	NM_201567.2		c.429+2129G>C		intron	N/A	NP_963861.1	P30304-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC25A	ENST00000302506.8	TSL:1 MANE Select	c.470G>C	p.Arg157Pro	missense	Exon 6 of 15	ENSP00000303706.3	P30304-1
	CDC25A	ENST00000351231.7	TSL:1	c.429+2129G>C		intron	N/A	ENSP00000343166.3	P30304-2
	CDC25A	ENST00000880434.1		c.467G>C	p.Arg156Pro	missense	Exon 6 of 15	ENSP00000550493.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.5
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.20
Sift	Benign	0.28	T
Sift4G	Benign	0.23	T
Polyphen		1.0	D
Vest4		0.73
MutPred		0.61		Loss of solvent accessibility (P = 0.0111)
MVP		0.67
MPC		1.1
ClinPred		0.91	D
GERP RS		5.9
Varity_R		0.54
gMVP		0.40
Mutation Taster		=57/43	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: rs372655408; hg19: chr3-48222290;