Variant 3-194341948-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001080513.4(CPN2):c.755C>T(p.Ala252Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00196 in 1,613,962 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 5 hom. )

Consequence

CPN2
NM_001080513.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.533

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008619219).

BP6

Variant 3-194341948-G-A is Benign according to our data. Variant chr3-194341948-G-A is described in ClinVar as [Benign]. Clinvar id is 790446.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CPN2	NM_001080513.4 linkuse as main transcript	c.755C>T	p.Ala252Val	missense_variant	2/2	ENST00000323830.4
CPN2	NM_001291988.2 linkuse as main transcript	c.755C>T	p.Ala252Val	missense_variant	2/2
CPN2	XM_005269280.5 linkuse as main transcript	c.755C>T	p.Ala252Val	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPN2	ENST00000323830.4 linkuse as main transcript	c.755C>T	p.Ala252Val	missense_variant	2/2	1	NM_001080513.4	P1
CPN2	ENST00000429275.1 linkuse as main transcript	c.755C>T	p.Ala252Val	missense_variant	2/2	5		P1

Frequencies

GnomAD3 genomes

AF:

0.00195

AC:

297

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00829

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00210

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00164

AC:

412

AN:

250600

Hom.:

AF XY:

0.00159

AC XY:

216

AN XY:

135656

show subpopulations

Gnomad AFR exome

AF:

0.000249

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.000795

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00797

Gnomad NFE exome

AF:

0.00174

Gnomad OTH exome

AF:

0.00229

GnomAD4 exome

AF:

0.00196

AC:

2872

AN:

1461648

Hom.:

Cov.:

AF XY:

0.00190

AC XY:

1382

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000805

Gnomad4 ASJ exome

AF:

0.000957

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00879

Gnomad4 NFE exome

AF:

0.00199

Gnomad4 OTH exome

AF:

0.00181

GnomAD4 genome

AF:

0.00195

AC:

297

AN:

152314

Hom.:

Cov.:

AF XY:

0.00223

AC XY:

166

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00274

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00829

Gnomad4 NFE

AF:

0.00210

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00171

Hom.:

Bravo

AF:

0.00172

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.00153

AC:

186

EpiCase

AF:

0.00158

EpiControl

AF:

0.00130

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.63

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.19

T;T

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.12

M_CAP

Benign

0.0078

MetaRNN

Benign

0.0086

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.80

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.10

Sift

Benign

0.16

T;T

Sift4G

Benign

0.13

T;T

Polyphen

0.38

B;B

Vest4

0.16

MVP

0.51

MPC

0.26

ClinPred

0.040

GERP RS

5.0

Varity_R

0.063

gMVP

0.24

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