Variant 3-194341266-G-C 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_001080513.4(CPN2):c.1437C>G(p.Ser479Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000231 in 1,613,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

CPN2
NM_001080513.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.83

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:

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=0.04440713).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CPN2	NM_001080513.4 linkuse as main transcript	c.1437C>G	p.Ser479Arg	missense_variant	2/2	ENST00000323830.4	NP_001073982.3
CPN2	NM_001291988.2 linkuse as main transcript	c.1437C>G	p.Ser479Arg	missense_variant	2/2		NP_001278917.1
CPN2	XM_005269280.5 linkuse as main transcript	c.1437C>G	p.Ser479Arg	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.1437C>G	p.Ser479Arg	missense_variant	2/2	1	NM_001080513.4	ENSP00000319464	P1
CPN2	ENST00000429275.1 linkuse as main transcript	c.1437C>G	p.Ser479Arg	missense_variant	2/2	5		ENSP00000402232	P1

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

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:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000200

AC:

AN:

250386

Hom.:

AF XY:

0.000251

AC XY:

AN XY:

135510

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000232

Gnomad NFE exome

AF:

0.000363

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000236

AC:

345

AN:

1461024

Hom.:

Cov.:

AF XY:

0.000233

AC XY:

169

AN XY:

726832

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000341

Gnomad4 NFE exome

AF:

0.000281

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000184

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000227

Hom.:

Bravo

AF:

0.000159

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000288

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000415

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

May 21, 2024

The c.1437C>G (p.S479R) 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 1437, causing the serine (S) at amino acid position 479 to be replaced by an arginine (R). 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

0.14

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.24

T;T

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.39

.;T

M_CAP

Benign

0.0078

MetaRNN

Benign

0.044

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.034

Sift

Benign

0.087

T;T

Sift4G

Benign

0.13

T;T

Polyphen

0.011

B;B

Vest4

0.11

MutPred

0.34

Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);

MVP

0.61

MPC

0.21

ClinPred

0.033

GERP RS

3.6

Varity_R

0.16

gMVP

0.62

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