11-57387853-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002728.6(PRG2):c.511C>T(p.Arg171Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000152 in 1,569,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

PRG2
NM_002728.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.359

Variant links:

Genes affected

PRG2 (HGNC:9362): (proteoglycan 2, pro eosinophil major basic protein) The protein encoded by this gene is the predominant constituent of the crystalline core of the eosinophil granule. High levels of the proform of this protein are also present in placenta and pregnancy serum, where it exists as a complex with several other proteins including pregnancy-associated plasma protein A (PAPPA), angiotensinogen (AGT), and C3dg. This protein may be involved in antiparasitic defense mechanisms as a cytotoxin and helminthotoxin, and in immune hypersensitivity reactions. The encoded protein contains a peptide that displays potent antimicrobial activity against Gram-positive bacteria, Gram-negative bacteria, and fungi. It is directly implicated in epithelial cell damage, exfoliation, and bronchospasm in allergic diseases. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2014]

PRG2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1460413).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PRG2	NM_002728.6 linkuse as main transcript	c.511C>T	p.Arg171Cys	missense_variant	5/6	ENST00000311862.10
PRG2	NM_001302926.2 linkuse as main transcript	c.511C>T	p.Arg171Cys	missense_variant	5/6
PRG2	NM_001302927.2 linkuse as main transcript	c.511C>T	p.Arg171Cys	missense_variant	5/6
PRG2	NM_001243245.3 linkuse as main transcript	c.478C>T	p.Arg160Cys	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRG2	ENST00000311862.10 linkuse as main transcript	c.511C>T	p.Arg171Cys	missense_variant	5/6	1	NM_002728.6	P1	P13727-1
PRG2	ENST00000525955.1 linkuse as main transcript	c.511C>T	p.Arg171Cys	missense_variant	5/6	2		P1	P13727-1
PRG2	ENST00000533605.5 linkuse as main transcript	c.478C>T	p.Arg160Cys	missense_variant	5/6	5			P13727-2
PRG2	ENST00000530105.1 linkuse as main transcript	n.858C>T		non_coding_transcript_exon_variant	4/5	5

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000250

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000140

AC:

AN:

178344

Hom.:

AF XY:

0.000116

AC XY:

AN XY:

94496

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000118

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000420

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000282

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000157

AC:

222

AN:

1417276

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

700438

show subpopulations

Gnomad4 AFR exome

AF:

0.0000907

Gnomad4 AMR exome

AF:

0.000109

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000498

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000187

Gnomad4 OTH exome

AF:

0.000102

GnomAD4 genome

AF:

0.000112

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000189

Hom.:

Bravo

AF:

0.000128

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000848

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 11, 2024

The c.511C>T (p.R171C) alteration is located in exon 5 (coding exon 4) of the PRG2 gene. This alteration results from a C to T substitution at nucleotide position 511, causing the arginine (R) at amino acid position 171 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.49

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.34

T;.;T

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.028

M_CAP

Benign

0.021

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.7

M;.;M

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Pathogenic

-5.8

D;D;D

REVEL

Benign

0.11

Sift

Uncertain

0.0010

D;D;D

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

0.60

P;.;P

Vest4

0.15

MVP

0.62

MPC

0.064

ClinPred

0.23

GERP RS

0.27

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.45

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over