rs17554211

Variant names:

• chr3-142823607-G-T
• rs17554211
• NM_013363.4:c.874C>A

Variant summary

Our verdict is Benign. The variant received -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.

• 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
• Publications: 18 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013363.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCOLCE2	NM_013363.4	MANE Select	c.874C>A	p.Pro292Thr	missense	Exon 7 of 9	NP_037495.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCOLCE2	ENST00000295992.8	TSL:1 MANE Select	c.874C>A	p.Pro292Thr	missense	Exon 7 of 9	ENSP00000295992.3
	PCOLCE2	ENST00000648195.1		c.874C>A	p.Pro292Thr	missense	Exon 7 of 9	ENSP00000497763.1
	PCOLCE2	ENST00000470310.5	TSL:5	n.49C>A		non_coding_transcript_exon	Exon 2 of 6	ENSP00000419643.1

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

GnomAD2 exomes AF: 0.0725 AC: 18000 AN: 248438 AF XY: 0.0742

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 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

African (AFR) AF: 0.0166 AC: 550 AN: 33082

American (AMR) AF: 0.0595 AC: 2605 AN: 43808

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 3298 AN: 25914

East Asian (EAS) AF: 0.000328 AC: 13 AN: 39590

South Asian (SAS) AF: 0.0262 AC: 2224 AN: 84980

European-Finnish (FIN) AF: 0.0536 AC: 2860 AN: 53380

Middle Eastern (MID) AF: 0.125 AC: 715 AN: 5730

European-Non Finnish (NFE) AF: 0.107 AC: 117037 AN: 1093802

Other (OTH) AF: 0.0860 AC: 5130 AN: 59652

GnomAD4 genome AF: 0.0720 AC: 10961 AN: 152224 Hom.: 561 Cov.: 32 AF XY: 0.0684 AC XY: 5088 AN XY: 74422

African (AFR) AF: 0.0206 AC: 856 AN: 41544

American (AMR) AF: 0.0767 AC: 1172 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 429 AN: 3468

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5188

South Asian (SAS) AF: 0.0195 AC: 94 AN: 4826

European-Finnish (FIN) AF: 0.0467 AC: 494 AN: 10588

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7359 AN: 68010

Other (OTH) AF: 0.0939 AC: 198 AN: 2108

Alfa AF: 0.0945 Hom.: 1707

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 v4.9

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
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		6.6
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
Mutation Taster		=80/20	polymorphism (auto)

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

Other links and lift over

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