4-15003168-C-A

Variant names:

• chr4-15003168-C-A
• NM_001177382.2:c.495C>A

Variant summary

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

The NM_001177382.2(CPEB2):​c.495C>A​(p.Asp165Glu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: CPEB2 NM_001177382.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.299

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]

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=0.1684848).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPEB2	NM_001177382.2	c.495C>A	p.Asp165Glu	missense_variant	Exon 1 of 12	ENST00000538197.7	NP_001170853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPEB2	ENST00000538197.7	c.495C>A	p.Asp165Glu	missense_variant	Exon 1 of 12	5	NM_001177382.2	ENSP00000443985.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 14, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.495C>A (p.D165E) alteration is located in exon 1 (coding exon 1) of the CPEB2 gene. This alteration results from a C to A substitution at nucleotide position 495, causing the aspartic acid (D) at amino acid position 165 to be replaced by a glutamic acid (E). 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	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Uncertain	23
DANN	Uncertain	0.99
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.16	N
M_CAP	Pathogenic	0.61	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.46	N;N
REVEL	Benign	0.036
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.44	T;T
Vest4		0.098
MutPred		0.10		Gain of helix (P = 0.0496);Gain of helix (P = 0.0496);
MVP		0.28
MPC		0.30
ClinPred		0.55	D
GERP RS		2.9
gMVP		0.0089

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-15004792;