Genetic Variant CPEB2:p.Ala73Glu (chr4-15002891-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001177382.2(CPEB2):c.218C>A(p.Ala73Glu) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A73G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CPEB2
NM_001177382.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.03

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2030012).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001177382.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CPEB2	NM_001177382.2	MANE Select	c.218C>A	p.Ala73Glu	missense	Exon 1 of 12	NP_001170853.1	Q7Z5Q1-9
CPEB2	NM_182485.3		c.218C>A	p.Ala73Glu	missense	Exon 1 of 11	NP_872291.2	A0A5K1VW93
CPEB2	NM_001177381.2		c.218C>A	p.Ala73Glu	missense	Exon 1 of 11	NP_001170852.1	Q7Z5Q1-8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CPEB2	ENST00000538197.7	TSL:5 MANE Select	c.218C>A	p.Ala73Glu	missense	Exon 1 of 12	ENSP00000443985.1	Q7Z5Q1-9
CPEB2	ENST00000507071.6	TSL:1	c.218C>A	p.Ala73Glu	missense	Exon 1 of 11	ENSP00000424084.2	A0A5K1VW93
CPEB2	ENST00000382395.8	TSL:1	c.218C>A	p.Ala73Glu	missense	Exon 1 of 11	ENSP00000371832.4	A0A5K1VW71

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1359458

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

670890

African (AFR)

AF:

0.00

AC:

AN:

29430

American (AMR)

AF:

0.00

AC:

AN:

27252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23966

East Asian (EAS)

AF:

0.00

AC:

AN:

35598

South Asian (SAS)

AF:

0.00

AC:

AN:

75920

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33102

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4938

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1072632

Other (OTH)

AF:

0.00

AC:

AN:

56620

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.97

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.29

M_CAP

Pathogenic

0.69

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.99

PhyloP100

2.0

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.50

REVEL

Benign

0.037

Sift

Uncertain

0.0010

Sift4G

Benign

0.096

Vest4

0.20

MutPred

0.26

Gain of solvent accessibility (P = 0.005)

MVP

0.25

MPC

0.37

ClinPred

0.58

GERP RS

1.9

PromoterAI

-0.10

Neutral

(source)

gMVP

0.086

Mutation Taster

=89/11

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over