Genetic Variant PCOLCE2:c.448+29A>G (chr3-142848188-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_013363.4(PCOLCE2):c.448+29A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0561 in 1,605,068 control chromosomes in the GnomAD database, including 2,776 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 0.056 ( 249 hom., cov: 33)

Exomes 𝑓: 0.056 ( 2527 hom. )

Consequence

PCOLCE2
NM_013363.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.272

Publications

5 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCOLCE2	NM_013363.4 link	c.448+29A>G		intron_variant	Intron 3 of 8	ENST00000295992.8	NP_037495.1	Q9UKZ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCOLCE2	ENST00000295992.8 link	c.448+29A>G		intron_variant	Intron 3 of 8	1	NM_013363.4	ENSP00000295992.3		Q9UKZ9

Frequencies

GnomAD3 genomes

AF:

0.0562

AC:

8555

AN:

152194

Hom.:

250

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0501

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.0535

Gnomad ASJ

AF:

0.0761

Gnomad EAS

AF:

0.0557

Gnomad SAS

AF:

0.106

Gnomad FIN

AF:

0.0657

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0538

Gnomad OTH

AF:

0.0828

GnomAD2 exomes

AF:

0.0577

AC:

14357

AN:

248864

AF XY:

0.0613

show subpopulations

Gnomad AFR exome

AF:

0.0488

Gnomad AMR exome

AF:

0.0346

Gnomad ASJ exome

AF:

0.0727

Gnomad EAS exome

AF:

0.0529

Gnomad FIN exome

AF:

0.0673

Gnomad NFE exome

AF:

0.0521

Gnomad OTH exome

AF:

0.0642

GnomAD4 exome

AF:

0.0561

AC:

81494

AN:

1452756

Hom.:

2527

Cov.:

AF XY:

0.0578

AC XY:

41717

AN XY:

721244

show subpopulations

African (AFR)

AF:

0.0476

AC:

1586

AN:

33318

American (AMR)

AF:

0.0382

AC:

1701

AN:

44480

Ashkenazi Jewish (ASJ)

AF:

0.0716

AC:

1853

AN:

25862

East Asian (EAS)

AF:

0.0556

AC:

2196

AN:

39502

South Asian (SAS)

AF:

0.0975

AC:

8348

AN:

85638

European-Finnish (FIN)

AF:

0.0675

AC:

3594

AN:

53244

Middle Eastern (MID)

AF:

0.0812

AC:

465

AN:

5730

European-Non Finnish (NFE)

AF:

0.0526

AC:

58117

AN:

1104954

Other (OTH)

AF:

0.0605

AC:

3634

AN:

60028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

3689

7379

11068

14758

18447

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0562

AC:

8555

AN:

152312

Hom.:

249

Cov.:

AF XY:

0.0573

AC XY:

4269

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0502

AC:

2084

AN:

41552

American (AMR)

AF:

0.0534

AC:

817

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0761

AC:

264

AN:

3468

East Asian (EAS)

AF:

0.0559

AC:

290

AN:

5190

South Asian (SAS)

AF:

0.105

AC:

508

AN:

4824

European-Finnish (FIN)

AF:

0.0657

AC:

698

AN:

10622

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0538

AC:

3661

AN:

68032

Other (OTH)

AF:

0.0814

AC:

172

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

437

874

1311

1748

2185

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0568

Hom.:

438

Bravo

AF:

0.0542

Asia WGS

AF:

0.0560

AC:

194

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

6.3

(source)

DANN

Benign

0.55

PhyloP100

-0.27

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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3-142848188-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over