Genetic Variant CDC25A:p.Val219Leu (chr3-48177883-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001789.3(CDC25A):c.655G>T(p.Val219Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. V219M) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

CDC25A
NM_001789.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.25

Publications

0 publications found

Variant links:

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]

CDC25A links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05088663).

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.655G>T	p.Val219Leu	missense	Exon 7 of 15	NP_001780.2
	CDC25A	NM_201567.2		c.535G>T	p.Val179Leu	missense	Exon 6 of 14	NP_963861.1	P30304-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDC25A	ENST00000302506.8	TSL:1 MANE Select	c.655G>T	p.Val219Leu	missense	Exon 7 of 15	ENSP00000303706.3	P30304-1
CDC25A	ENST00000351231.7	TSL:1	c.535G>T	p.Val179Leu	missense	Exon 6 of 14	ENSP00000343166.3	P30304-2
CDC25A	ENST00000880434.1		c.652G>T	p.Val218Leu	missense	Exon 7 of 15	ENSP00000550493.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251448

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.57

CADD

Benign

9.9

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.086

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.58

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0087

MetaRNN

Benign

0.051

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.45

PhyloP100

1.2

PrimateAI

Benign

0.31

PROVEAN

Benign

0.42

REVEL

Benign

0.050

Sift

Benign

0.67

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.12

MutPred

0.52

Gain of relative solvent accessibility (P = 0.0479)

MVP

0.21

MPC

0.25

ClinPred

0.033

GERP RS

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.022

gMVP

0.080

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over