Genetic Variant PCOLCE2:p.Thr275Ser (chr3-142829733-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_013363.4(PCOLCE2):c.824C>G(p.Thr275Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000994 in 1,609,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

PCOLCE2
NM_013363.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.43

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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18894693).

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.824C>G	p.Thr275Ser	missense	Exon 6 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.824C>G	p.Thr275Ser	missense	Exon 6 of 9	ENSP00000295992.3	Q9UKZ9
PCOLCE2	ENST00000964680.1		c.881C>G	p.Thr294Ser	missense	Exon 7 of 10	ENSP00000634739.1
PCOLCE2	ENST00000964678.1		c.824C>G	p.Thr275Ser	missense	Exon 6 of 9	ENSP00000634737.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000280

AC:

AN:

249590

AF XY:

0.0000222

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000206

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:

0.00000892

AC:

AN:

1457008

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

724686

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33396

American (AMR)

AF:

0.000292

AC:

AN:

44466

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25996

East Asian (EAS)

AF:

0.00

AC:

AN:

39580

South Asian (SAS)

AF:

0.00

AC:

AN:

85124

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53164

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109406

Other (OTH)

AF:

0.00

AC:

AN:

60130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

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

AF:

0.0000197

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41412

American (AMR)

AF:

0.000196

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.030

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.15

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.68

M_CAP

Benign

0.016

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

7.4

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.24

REVEL

Benign

0.19

Sift

Benign

0.41

Sift4G

Benign

0.58

Polyphen

0.085

Vest4

0.53

MutPred

0.26

Loss of glycosylation at T274 (P = 0.0958)

MVP

0.21

MPC

0.14

ClinPred

0.13

GERP RS

5.3

Varity_R

0.12

gMVP

0.32

Mutation Taster

=28/72

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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