Variant 4-15003101-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001177382.2(CPEB2):c.428G>C(p.Ser143Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,382,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CPEB2
NM_001177382.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.47

Variant links:

Genes affected

CPEB2 (HGNC:21745): (cytoplasmic polyadenylation element binding protein 2) The protein encoded by this gene is highly similar to cytoplasmic polyadenylation element binding protein (CPEB), an mRNA-binding protein that regulates cytoplasmic polyadenylation of mRNA as a trans factor in oogenesis and spermatogenesis. Studies of the similar gene in mice suggested a possible role of this protein in transcriptionally inactive haploid spermatids. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

CPEB2 links:

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ACMG classification

Classification made for transcript

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=0.13491973).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPEB2	NM_001177382.2 link	c.428G>C	p.Ser143Thr	missense_variant	1/12	ENST00000538197.7	NP_001170853.1	Q7Z5Q1-9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPEB2	ENST00000538197.7 link	c.428G>C	p.Ser143Thr	missense_variant	1/12	5	NM_001177382.2	ENSP00000443985.1		Q7Z5Q1-9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000764

AC:

AN:

130812

Hom.:

AF XY:

0.00

AC XY:

AN XY:

71404

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000414

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000145

AC:

AN:

1382050

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

682010

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000282

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.27e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 11, 2022

The c.428G>C (p.S143T) alteration is located in exon 1 (coding exon 1) of the CPEB2 gene. This alteration results from a G to C substitution at nucleotide position 428, causing the serine (S) at amino acid position 143 to be replaced by a threonine (T). 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

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.093

FATHMM_MKL

Benign

0.43

M_CAP

Pathogenic

0.49

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.34

N;N

REVEL

Benign

0.067

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.85

T;T

Vest4

0.10

MutPred

0.080

Gain of glycosylation at S143 (P = 0.0424);Gain of glycosylation at S143 (P = 0.0424);

MVP

0.32

MPC

0.29

ClinPred

0.40

GERP RS

2.9

gMVP

0.021

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over