3-142880978-C-T

Variant summary

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

The NM_013363.4(PCOLCE2):c.192+6691G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 152,156 control chromosomes in the GnomAD database, including 50,571 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 0.81 (50571 hom., cov: 32)
• Consequence: PCOLCE2 NM_013363.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCOLCE2	NM_013363.4	c.192+6691G>A		intron_variant		ENST00000295992.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCOLCE2	ENST00000295992.8	c.192+6691G>A		intron_variant		1	NM_013363.4	P1

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123493 AN: 152038 Hom.: 50520 Cov.: 32

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.887

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.852

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.791

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.812 AC: 123599 AN: 152156 Hom.: 50571 Cov.: 32 AF XY: 0.812 AC XY: 60458 AN XY: 74420

Gnomad4 AFR AF: 0.898

Gnomad4 AMR AF: 0.746

Gnomad4 ASJ AF: 0.821

Gnomad4 EAS AF: 0.769

Gnomad4 SAS AF: 0.635

Gnomad4 FIN AF: 0.852

Gnomad4 NFE AF: 0.784

Gnomad4 OTH AF: 0.794

Alfa AF: 0.788 Hom.: 7482

Bravo AF: 0.810

Asia WGS AF: 0.720 AC: 2502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	7.8
Dann	Benign	0.81

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: rs2707985; hg19: chr3-142599820;