chr3-48164371-T-C

Variant names:

• chr3-48164371-T-C
• rs2031914651
• NM_001789.3:c.1258A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001789.3(CDC25A):​c.1258A>G​(p.Thr420Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,452,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CDC25A NM_001789.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.478
• 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]

ENSG00000302863 (HGNC:):

ACMG classification

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=0.029295862).

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.1258A>G	p.Thr420Ala	missense	Exon 13 of 15	NP_001780.2
	CDC25A	NM_201567.2		c.1138A>G	p.Thr380Ala	missense	Exon 12 of 14	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.1258A>G	p.Thr420Ala	missense	Exon 13 of 15	ENSP00000303706.3	P30304-1
	CDC25A	ENST00000351231.7	TSL:1	c.1138A>G	p.Thr380Ala	missense	Exon 12 of 14	ENSP00000343166.3	P30304-2
	CDC25A	ENST00000880434.1		c.1255A>G	p.Thr419Ala	missense	Exon 13 of 15	ENSP00000550493.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1452318 Hom.: 0 Cov.: 30 AF XY: 0.00000415 AC XY: 3 AN XY: 722480

African (AFR) AF: 0.00 AC: 0 AN: 32868

American (AMR) AF: 0.00 AC: 0 AN: 42436

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25968

East Asian (EAS) AF: 0.00 AC: 0 AN: 38998

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 84290

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1108692

Other (OTH) AF: 0.00 AC: 0 AN: 59982

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

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	0.059
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	13
DANN	Benign	0.79
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.33	N
PhyloP100		0.48
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.014
Sift	Benign	0.44	T
Sift4G	Benign	0.73	T
Polyphen		0.0	B
Vest4		0.071
MutPred		0.31		Gain of sheet (P = 0.0221)
MVP		0.28
MPC		1.1
ClinPred		0.055	T
GERP RS		1.7
Varity_R		0.034
gMVP		0.66
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

dbSNP: rs2031914651; hg19: chr3-48205861;