5-138329634-G-T

Position:

• chr5-138329634-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001790.5(CDC25C):​c.208C>A​(p.Arg70Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R70C) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CDC25C NM_001790.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.809

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07318735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC25C	NM_001790.5	c.208C>A	p.Arg70Ser	missense_variant	3/14	ENST00000323760.11	NP_001781.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC25C	ENST00000323760.11	c.208C>A	p.Arg70Ser	missense_variant	3/14	1	NM_001790.5	ENSP00000321656	P2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	10
DANN	Benign	0.93
DEOGEN2	Benign	0.28	T;T;.;.;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.74	.;T;T;T;T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.073	T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.9	L;L;L;.;.
MutationTaster	Benign	1.0	P;P;P;P;P;P;P
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.78	N;N;N;N;N
REVEL	Benign	0.088
Sift	Benign	0.32	T;T;T;T;T
Sift4G	Benign	0.12	T;T;T;T;T
Polyphen		0.50	P;P;B;.;.
Vest4		0.22
MutPred		0.22		Gain of phosphorylation at R70 (P = 0.0449);Gain of phosphorylation at R70 (P = 0.0449);Gain of phosphorylation at R70 (P = 0.0449);Gain of phosphorylation at R70 (P = 0.0449);.;
MVP		0.35
MPC		0.29
ClinPred		0.39	T
GERP RS		-0.96
Varity_R		0.10
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs3734166; hg19: chr5-137665323;