Variant chr3-194341769-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000323830.4(CPN2):c.934C>G(p.Leu312Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,198 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

CPN2
ENST00000323830.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.23

Variant links:

Genes affected

CPN2 (HGNC:2313): (carboxypeptidase N subunit 2) Predicted to be involved in regulation of catalytic activity. Located in blood microparticle and extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

CPN2 links:

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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
CPN2	NM_001080513.4 linkuse as main transcript	c.934C>G	p.Leu312Val	missense_variant	2/2	ENST00000323830.4	NP_001073982.3
CPN2	NM_001291988.2 linkuse as main transcript	c.934C>G	p.Leu312Val	missense_variant	2/2		NP_001278917.1
CPN2	XM_005269280.5 linkuse as main transcript	c.934C>G	p.Leu312Val	missense_variant	3/3		XP_005269337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPN2	ENST00000323830.4 linkuse as main transcript	c.934C>G	p.Leu312Val	missense_variant	2/2	1	NM_001080513.4	ENSP00000319464	P1
CPN2	ENST00000429275.1 linkuse as main transcript	c.934C>G	p.Leu312Val	missense_variant	2/2	5		ENSP00000402232	P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.000479

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.00

Gnomad4 OTH

AF:

0.000479

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

Jan 18, 2023

The c.934C>G (p.L312V) alteration is located in exon 2 (coding exon 1) of the CPN2 gene. This alteration results from a C to G substitution at nucleotide position 934, causing the leucine (L) at amino acid position 312 to be replaced by a valine (V). 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

0.12

BayesDel_addAF

Benign

-0.0096

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

T;T

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.46

.;T

M_CAP

Benign

0.051

MetaRNN

Uncertain

0.68

D;D

MetaSVM

Uncertain

-0.26

MutationAssessor

Benign

1.9

L;L

MutationTaster

Benign

0.92

D;D

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-2.7

D;D

REVEL

Uncertain

0.46

Sift

Benign

0.11

T;T

Sift4G

Uncertain

0.027

D;D

Polyphen

0.99

D;D

Vest4

0.49

MutPred

0.58

Gain of catalytic residue at L312 (P = 0.0398);Gain of catalytic residue at L312 (P = 0.0398);

MVP

0.85

MPC

0.74

ClinPred

0.86

GERP RS

2.4

Varity_R

0.45

gMVP

0.60

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