Genetic Variant PCOLCE2:p.Gly134Ala (chr3-142848264-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_013363.4(PCOLCE2):c.401G>C(p.Gly134Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G134D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

PCOLCE2
NM_013363.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.39

Publications

0 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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCOLCE2	NM_013363.4	MANE Select	c.401G>C	p.Gly134Ala	missense	Exon 3 of 9	NP_037495.1	Q9UKZ9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PCOLCE2	ENST00000295992.8	TSL:1 MANE Select	c.401G>C	p.Gly134Ala	missense	Exon 3 of 9	ENSP00000295992.3	Q9UKZ9
PCOLCE2	ENST00000964680.1		c.401G>C	p.Gly134Ala	missense	Exon 3 of 10	ENSP00000634739.1
PCOLCE2	ENST00000964678.1		c.401G>C	p.Gly134Ala	missense	Exon 3 of 9	ENSP00000634737.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000199

AC:

AN:

251450

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33478

American (AMR)

AF:

0.000112

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111976

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

0.0083

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

(source)

DANN

Benign

0.45

DEOGEN2

Benign

0.15

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.016

MetaRNN

Uncertain

0.74

MetaSVM

Benign

-1.2

MutationAssessor

Benign

0.92

PhyloP100

7.4

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-4.0

REVEL

Uncertain

0.35

Sift

Benign

0.082

Sift4G

Uncertain

0.051

Polyphen

0.74

Vest4

0.89

MutPred

0.59

Loss of catalytic residue at G134 (P = 0.1424)

MVP

0.29

MPC

0.56

ClinPred

0.87

GERP RS

5.3

Varity_R

0.46

gMVP

0.61

Mutation Taster

=9/91

disease causing

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over