3-48177870-T-A

Variant summary

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

The NM_001789.3(CDC25A):​c.668A>T​(p.Asp223Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CDC25A
NM_001789.3 missense

Scores

1
9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.53
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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/exons MANE Protein UniProt
CDC25ANM_001789.3 linkuse as main transcriptc.668A>T p.Asp223Val missense_variant 7/15 ENST00000302506.8 NP_001780.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CDC25AENST00000302506.8 linkuse as main transcriptc.668A>T p.Asp223Val missense_variant 7/151 NM_001789.3 ENSP00000303706 P1P30304-1
CDC25AENST00000351231.7 linkuse as main transcriptc.548A>T p.Asp183Val missense_variant 6/141 ENSP00000343166 P30304-2
CDC25AENST00000443342.5 linkuse as main transcriptc.665A>T p.Asp222Val missense_variant 7/83 ENSP00000416483

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 12, 2023The c.668A>T (p.D223V) alteration is located in exon 7 (coding exon 7) of the CDC25A gene. This alteration results from a A to T substitution at nucleotide position 668, causing the aspartic acid (D) at amino acid position 223 to be replaced by a valine (V). 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
0.34
BayesDel_addAF
Benign
-0.0063
T
BayesDel_noAF
Benign
-0.25
CADD
Uncertain
26
DANN
Uncertain
0.98
DEOGEN2
Benign
0.39
T;.;T
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.92
D;D;D
M_CAP
Benign
0.031
D
MetaRNN
Uncertain
0.57
D;D;D
MetaSVM
Benign
-0.96
T
MutationAssessor
Pathogenic
3.1
M;.;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Benign
0.42
T
PROVEAN
Uncertain
-4.1
D;D;D
REVEL
Benign
0.24
Sift
Uncertain
0.0020
D;D;D
Sift4G
Uncertain
0.0040
D;D;.
Polyphen
0.58
P;P;.
Vest4
0.47
MutPred
0.60
Loss of disorder (P = 0.0155);.;.;
MVP
0.44
MPC
0.89
ClinPred
0.98
D
GERP RS
5.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.48
gMVP
0.53

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-48219360; API