chr4-15040478-C-G

Position:

• chr4-15040478-C-G

Variant summary

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

The NM_001177382.2(CPEB2):​c.2191C>G​(p.Arg731Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPEB2 NM_001177382.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.61

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]

C1QTNF7-AS1 (HGNC:40683): (C1QTNF7 antisense RNA 1)

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
CPEB2	NM_001177382.2	c.2191C>G	p.Arg731Gly	missense_variant	6/12	ENST00000538197.7	NP_001170853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPEB2	ENST00000538197.7	c.2191C>G	p.Arg731Gly	missense_variant	6/12	5	NM_001177382.2	ENSP00000443985.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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

Dec 05, 2024

The c.2191C>G (p.R731G) alteration is located in exon 6 (coding exon 6) of the CPEB2 gene. This alteration results from a C to G substitution at nucleotide position 2191, causing the arginine (R) at amino acid position 731 to be replaced by a glycine (G). 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	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Pathogenic	27
DANN	Uncertain	1.0
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.86	D
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.44	T;T;T;T
MetaSVM	Benign	-0.31	T
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-2.9	D;D;D;N
REVEL	Benign	0.17
Sift	Uncertain	0.014	D;D;D;D
Sift4G	Benign	0.084	T;T;T;T
Polyphen		0.99	.;.;.;D
Vest4		0.55
MutPred		0.34		Loss of methylation at R731 (P = 0.013);.;.;.;
MVP		0.51
MPC		2.6
ClinPred		0.99	D
GERP RS		4.9
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs369762245; hg19: chr4-15042102;