rs3731562

chr3-48158387-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001789.3(CDC25A):c.*558C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00503 in 151,152 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0050 (8 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDC25A NM_001789.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.79

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00503 (761/151152) while in subpopulation SAS AF= 0.0492 (236/4792). AF 95% confidence interval is 0.0441. There are 8 homozygotes in gnomad4. There are 416 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 760 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDC25A	NM_001789.3	c.*558C>T		3_prime_UTR_variant	15/15	ENST00000302506.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC25A	ENST00000302506.8	c.*558C>T		3_prime_UTR_variant	15/15	1	NM_001789.3	P1
CDC25A	ENST00000351231.7	c.*558C>T		3_prime_UTR_variant	14/14	1

Frequencies

GnomAD3 genomes AF: 0.00503 AC: 760 AN: 151038 Hom.: 8 Cov.: 31

Gnomad AFR AF: 0.00868

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00152

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.0226

Gnomad SAS AF: 0.0492

Gnomad FIN AF: 0.0000978

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00481

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 420 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 258

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00503 AC: 761 AN: 151152 Hom.: 8 Cov.: 31 AF XY: 0.00564 AC XY: 416 AN XY: 73744

Gnomad4 AFR AF: 0.00867

Gnomad4 AMR AF: 0.00152

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.0227

Gnomad4 SAS AF: 0.0492

Gnomad4 FIN AF: 0.0000978

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00476

Alfa AF: 0.00334 Hom.: 1

Bravo AF: 0.00416

Asia WGS AF: 0.0280 AC: 97 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	17
Dann	Benign	0.62

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

LitVar

Other links and lift over

dbSNP: rs3731562; hg19: chr3-48199877;