chr3-48158205-T-C

Position:

• chr3-48158205-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001789.3(CDC25A):​c.*740A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00915 in 152,730 control chromosomes in the GnomAD database, including 9 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 0.0092 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (0 hom.)
• Consequence: CDC25A NM_001789.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.665

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BS2: High AC in GnomAd4 at 1396 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC25A	NM_001789.3	c.*740A>G		3_prime_UTR_variant	15/15	ENST00000302506.8	NP_001780.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC25A	ENST00000302506.8	c.*740A>G		3_prime_UTR_variant	15/15	1	NM_001789.3	ENSP00000303706	P1
CDC25A	ENST00000351231.7	c.*740A>G		3_prime_UTR_variant	14/14	1		ENSP00000343166

Frequencies

GnomAD3 genomes AF: 0.00918 AC: 1397 AN: 152152 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00220

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00786

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0122

Gnomad FIN AF: 0.00838

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0148

Gnomad OTH AF: 0.00669

GnomAD4 exome AF: 0.00217 AC: 1 AN: 460 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 278

Gnomad4 FIN exome AF: 0.00236

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00917 AC: 1396 AN: 152270 Hom.: 9 Cov.: 32 AF XY: 0.00935 AC XY: 696 AN XY: 74460

Gnomad4 AFR AF: 0.00219

Gnomad4 AMR AF: 0.00778

Gnomad4 ASJ AF: 0.00404

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0122

Gnomad4 FIN AF: 0.00838

Gnomad4 NFE AF: 0.0148

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.0128 Hom.: 5

Bravo AF: 0.00881

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	13
DANN	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs3731563; hg19: chr3-48199695;