5-138286042-C-A

Position:

• chr5-138286042-C-A

Variant summary

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

The NM_001790.5(CDC25C):​c.1252G>T​(p.Asp418Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDC25C NM_001790.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.81

Genes affected

CDC25C (HGNC:1727): (cell division cycle 25C) This gene encodes a conserved protein that plays a key role in the regulation of cell division. The encoded protein directs dephosphorylation of cyclin B-bound CDC2 and triggers entry into mitosis. It also suppresses p53-induced growth arrest. Multiple alternatively spliced transcript variants of this gene have been described. [provided by RefSeq, Dec 2015]

ACMG classification

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
CDC25C	NM_001790.5	c.1252G>T	p.Asp418Tyr	missense_variant	13/14	ENST00000323760.11	NP_001781.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC25C	ENST00000323760.11	c.1252G>T	p.Asp418Tyr	missense_variant	13/14	1	NM_001790.5	ENSP00000321656.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 01, 2024

The c.1252G>T (p.D418Y) alteration is located in exon 13 (coding exon 12) of the CDC25C gene. This alteration results from a G to T substitution at nucleotide position 1252, causing the aspartic acid (D) at amino acid position 418 to be replaced by a tyrosine (Y). 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	0.23
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.42	T;.;.;T;.
Eigen	Benign	-0.054
Eigen_PC	Benign	-0.020
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.98	.;D;.;D;D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.72	D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M;.;.;M;.
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-5.9	D;D;D;D;D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0010	D;D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D;D
Polyphen		1.0	D;D;D;D;D
Vest4		0.68
MutPred		0.53		Gain of methylation at K413 (P = 0.0902);.;.;Gain of methylation at K413 (P = 0.0902);.;
MVP		0.50
MPC		0.77
ClinPred		0.99	D
GERP RS		3.3
Varity_R		0.80
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs759056350; hg19: chr5-137621731;