Variant rs17554211 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000295992.8(PCOLCE2):c.874C>A(p.Pro292Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0913 in 1,592,162 control chromosomes in the GnomAD database, including 7,789 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.072 ( 561 hom., cov: 32)

Exomes 𝑓: 0.093 ( 7228 hom. )

Consequence

PCOLCE2
ENST00000295992.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.55

Variant links:

Genes affected

PCOLCE2 (HGNC:8739): (procollagen C-endopeptidase enhancer 2) Enables collagen binding activity; heparin binding activity; and peptidase activator activity. Predicted to be involved in positive regulation of peptidase activity. Predicted to act upstream of or within cellular response to leukemia inhibitory factor. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

PCOLCE2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016604066).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCOLCE2	NM_013363.4 linkuse as main transcript	c.874C>A	p.Pro292Thr	missense_variant	7/9	ENST00000295992.8	NP_037495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCOLCE2	ENST00000295992.8 linkuse as main transcript	c.874C>A	p.Pro292Thr	missense_variant	7/9	1	NM_013363.4	ENSP00000295992	P1

Frequencies

GnomAD3 genomes

AF:

0.0721

AC:

10962

AN:

152106

Hom.:

561

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0207

Gnomad AMI

AF:

0.344

Gnomad AMR

AF:

0.0767

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0190

Gnomad FIN

AF:

0.0467

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.0954

GnomAD3 exomes

AF:

0.0725

AC:

18000

AN:

248438

Hom.:

928

AF XY:

0.0742

AC XY:

9959

AN XY:

134226

show subpopulations

Gnomad AFR exome

AF:

0.0182

Gnomad AMR exome

AF:

0.0573

Gnomad ASJ exome

AF:

0.132

Gnomad EAS exome

AF:

0.000329

Gnomad SAS exome

AF:

0.0233

Gnomad FIN exome

AF:

0.0514

Gnomad NFE exome

AF:

0.107

Gnomad OTH exome

AF:

0.0973

GnomAD4 exome

AF:

0.0934

AC:

134432

AN:

1439938

Hom.:

7228

Cov.:

AF XY:

0.0925

AC XY:

66367

AN XY:

717608

show subpopulations

Gnomad4 AFR exome

AF:

0.0166

Gnomad4 AMR exome

AF:

0.0595

Gnomad4 ASJ exome

AF:

0.127

Gnomad4 EAS exome

AF:

0.000328

Gnomad4 SAS exome

AF:

0.0262

Gnomad4 FIN exome

AF:

0.0536

Gnomad4 NFE exome

AF:

0.107

Gnomad4 OTH exome

AF:

0.0860

GnomAD4 genome

AF:

0.0720

AC:

10961

AN:

152224

Hom.:

561

Cov.:

AF XY:

0.0684

AC XY:

5088

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0206

Gnomad4 AMR

AF:

0.0767

Gnomad4 ASJ

AF:

0.124

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0195

Gnomad4 FIN

AF:

0.0467

Gnomad4 NFE

AF:

0.108

Gnomad4 OTH

AF:

0.0939

Alfa

AF:

0.0989

Hom.:

1182

Bravo

AF:

0.0745

TwinsUK

AF:

0.107

AC:

398

ALSPAC

AF:

0.102

AC:

393

ESP6500AA

AF:

0.0216

AC:

ESP6500EA

AF:

0.112

AC:

961

ExAC

AF:

0.0714

AC:

8668

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.120

EpiControl

AF:

0.126

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

T;.

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.85

T;T

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

0.010

P;P

PrimateAI

Uncertain

0.48

PROVEAN

Uncertain

-3.8

D;.

REVEL

Benign

0.19

Sift

Uncertain

0.025

D;.

Sift4G

Uncertain

0.036

D;.

Polyphen

0.0070

B;.

Vest4

0.20

MPC

0.18

ClinPred

0.040

GERP RS

5.4

Varity_R

0.39

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over