chr16-57121190-C-T

Variant summary

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

The NM_152727.6(CPNE2):​c.779C>T​(p.Pro260Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,613,102 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

CPNE2
NM_152727.6 missense, splice_region

Scores

2
4
13
Splicing: ADA: 0.8434
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.51
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]

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ACMG classification

Classification made for transcript

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
CPNE2NM_152727.6 linkuse as main transcriptc.779C>T p.Pro260Leu missense_variant, splice_region_variant 8/16 ENST00000290776.13 NP_689940.3 Q96FN4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CPNE2ENST00000290776.13 linkuse as main transcriptc.779C>T p.Pro260Leu missense_variant, splice_region_variant 8/161 NM_152727.6 ENSP00000290776.8 Q96FN4-1
CPNE2ENST00000535318.6 linkuse as main transcriptc.779C>T p.Pro260Leu missense_variant, splice_region_variant 9/171 ENSP00000439018.2 Q96FN4-1
CPNE2ENST00000565874.5 linkuse as main transcriptc.779C>T p.Pro260Leu missense_variant, splice_region_variant 7/151 ENSP00000456042.1 Q96FN4-1
CPNE2ENST00000565766.1 linkuse as main transcriptc.266C>T p.Pro89Leu missense_variant, splice_region_variant 3/105 ENSP00000457579.1 H3BUC8

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152154
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000282
AC:
7
AN:
248286
Hom.:
0
AF XY:
0.0000223
AC XY:
3
AN XY:
134424
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000656
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000270
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000157
AC:
23
AN:
1460948
Hom.:
0
Cov.:
30
AF XY:
0.0000193
AC XY:
14
AN XY:
726734
show subpopulations
Gnomad4 AFR exome
AF:
0.000179
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152154
Hom.:
0
Cov.:
32
AF XY:
0.0000807
AC XY:
6
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000132
Hom.:
0
Bravo
AF:
0.0000529
ExAC
AF:
0.0000412
AC:
5

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 submitterclinical testingAmbry GeneticsDec 20, 2023The c.779C>T (p.P260L) alteration is located in exon 8 (coding exon 7) of the CPNE2 gene. This alteration results from a C to T substitution at nucleotide position 779, causing the proline (P) at amino acid position 260 to be replaced by a leucine (L). 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
0.11
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.37
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.28
T;T;T
Eigen
Benign
0.026
Eigen_PC
Benign
0.15
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.92
.;.;D
M_CAP
Benign
0.019
T
MetaRNN
Uncertain
0.66
D;D;D
MetaSVM
Benign
-0.98
T
MutationAssessor
Uncertain
2.1
M;M;M
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Benign
0.44
T
PROVEAN
Pathogenic
-5.1
D;D;D
REVEL
Benign
0.088
Sift
Benign
0.045
D;D;D
Sift4G
Benign
0.080
T;T;T
Polyphen
0.017
B;B;B
Vest4
0.76
MVP
0.22
MPC
0.47
ClinPred
0.14
T
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.1
Varity_R
0.15
gMVP
0.34

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.84
dbscSNV1_RF
Benign
0.45
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.

Other links and lift over

dbSNP: rs775368038; hg19: chr16-57155102; API