chr3-142823607-G-T

Position:

• chr3-142823607-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013363.4(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 NM_013363.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.55

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 (HGNC:):

ACMG classification

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	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	c.874C>A	p.Pro292Thr	missense_variant	7/9	1	NM_013363.4	ENSP00000295992.3

Frequencies

GnomAD3 genomes AF: 0.0721 AC: 10962 AN: 152106 Hom.: 561 Cov.: 32

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

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.: 26 AF XY: 0.0925 AC XY: 66367 AN XY: 717608

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.: 32 AF XY: 0.0684 AC XY: 5088 AN XY: 74422

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: 95

ESP6500EA AF: 0.112 AC: 961

ExAC AF: 0.0714 AC: 8668

Asia WGS AF: 0.0140 AC: 48 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	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T;.
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.85	T;T
MetaRNN	Benign	0.0017	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Uncertain	0.48	T
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	T
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

Other links and lift over

dbSNP: rs17554211; hg19: chr3-142542449; COSMIC: COSV56000962; COSMIC: COSV56000962;