16-57110861-T-C

Position:

• chr16-57110861-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152727.6(CPNE2):​c.119T>C​(p.Val40Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CPNE2 NM_152727.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.82

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3172097).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPNE2	NM_152727.6	c.119T>C	p.Val40Ala	missense_variant	2/16	ENST00000290776.13	NP_689940.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPNE2	ENST00000290776.13	c.119T>C	p.Val40Ala	missense_variant	2/16	1	NM_152727.6	ENSP00000290776.8
CPNE2	ENST00000535318.6	c.119T>C	p.Val40Ala	missense_variant	3/17	1		ENSP00000439018.2
CPNE2	ENST00000565874.5	c.119T>C	p.Val40Ala	missense_variant	1/15	1		ENSP00000456042.1
CPNE2	ENST00000566259.1	c.119T>C	p.Val40Ala	missense_variant	2/3	3		ENSP00000455883.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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 21, 2023

The c.119T>C (p.V40A) alteration is located in exon 2 (coding exon 1) of the CPNE2 gene. This alteration results from a T to C substitution at nucleotide position 119, causing the valine (V) at amino acid position 40 to be replaced by an alanine (A). 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	Pathogenic	0.67
BayesDel_addAF	Benign	0.0074	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	22
DANN	Benign	0.89
DEOGEN2	Benign	0.12	T;T;.;T
Eigen	Benign	0.042
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.66	.;.;T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.32	T;T;T;T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.0	L;L;.;L
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.9	N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.36	T;T;T;T
Sift4G	Benign	0.32	T;T;T;T
Polyphen		0.025	B;B;.;B
Vest4		0.64
MutPred		0.41		Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);
MVP		0.35
MPC		0.54
ClinPred		0.56	D
GERP RS		5.3
Varity_R		0.13
gMVP		0.56

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: chr16-57144773;