Variant 16-57121178-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152727.6(CPNE2):c.767G>A(p.Arg256Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000175 in 1,613,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

CPNE2
NM_152727.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.37

Variant links:

Genes affected

CPNE2 (HGNC:2315): (copine 2) Calcium-dependent membrane-binding proteins may regulate molecular events at the interface of the cell membrane and cytoplasm. This gene is one of several genes that encode a calcium-dependent protein containing two N-terminal type II C2 domains and an integrin A domain-like sequence in the C-terminus. Sequence analysis identified multiple alternatively spliced transcript variants but their full-length natures could not be determined. [provided by RefSeq, Jul 2008]

CPNE2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.039437026).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPNE2	NM_152727.6 linkuse as main transcript	c.767G>A	p.Arg256Gln	missense_variant	8/16	ENST00000290776.13	NP_689940.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPNE2	ENST00000290776.13 linkuse as main transcript	c.767G>A	p.Arg256Gln	missense_variant	8/16	1	NM_152727.6	ENSP00000290776	P1	Q96FN4-1
CPNE2	ENST00000535318.6 linkuse as main transcript	c.767G>A	p.Arg256Gln	missense_variant	9/17	1		ENSP00000439018	P1	Q96FN4-1
CPNE2	ENST00000565874.5 linkuse as main transcript	c.767G>A	p.Arg256Gln	missense_variant	7/15	1		ENSP00000456042	P1	Q96FN4-1
CPNE2	ENST00000565766.1 linkuse as main transcript	c.257G>A	p.Arg86Gln	missense_variant	3/10	5		ENSP00000457579

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000120

AC:

AN:

249204

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

134896

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000152

Gnomad OTH exome

AF:

0.000655

GnomAD4 exome

AF:

0.000185

AC:

270

AN:

1461598

Hom.:

Cov.:

AF XY:

0.000184

AC XY:

134

AN XY:

727092

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000268

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:

0.000216

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.0000642

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

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

Dec 07, 2021

The c.767G>A (p.R256Q) alteration is located in exon 8 (coding exon 7) of the CPNE2 gene. This alteration results from a G to A substitution at nucleotide position 767, causing the arginine (R) at amino acid position 256 to be replaced by a glutamine (Q). 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

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.35

DEOGEN2

Benign

0.019

T;T;T

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.86

.;.;D

M_CAP

Benign

0.0058

MetaRNN

Benign

0.039

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.64

N;N;N

MutationTaster

Benign

0.60

D;N;N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

0.040

N;N;N

REVEL

Benign

0.023

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.94

T;T;T

Polyphen

0.0010

B;B;B

Vest4

0.23

MVP

0.22

MPC

0.51

ClinPred

0.027

GERP RS

2.5

Varity_R

0.031

gMVP

0.11

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