Genetic Variant NM_002728.6:c.235G>A (chr11-57389141-C-T) – 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_002728.6(PRG2):c.235G>A(p.Val79Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PRG2
NM_002728.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.448

Publications

0 publications found

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:

ENSG00000254979 (HGNC:):

ENSG00000254979 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_002728.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRG2	NM_002728.6	MANE Select	c.235G>A	p.Val79Met	missense	Exon 3 of 6	NP_002719.3
PRG2	NM_001302926.2		c.235G>A	p.Val79Met	missense	Exon 3 of 6	NP_001289855.1	P13727-1
PRG2	NM_001302927.2		c.235G>A	p.Val79Met	missense	Exon 3 of 6	NP_001289856.1	P13727-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRG2	ENST00000311862.10	TSL:1 MANE Select	c.235G>A	p.Val79Met	missense	Exon 3 of 6	ENSP00000312134.5	P13727-1
ENSG00000254979	ENST00000529411.1	TSL:4	c.550G>A	p.Val184Met	missense	Exon 4 of 4	ENSP00000431536.1	H0YCG3
PRG2	ENST00000525955.1	TSL:2	c.235G>A	p.Val79Met	missense	Exon 3 of 6	ENSP00000433016.1	P13727-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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

0.11

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.50

M_CAP

Benign

0.010

MetaRNN

Benign

0.091

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

0.45

PROVEAN

Benign

-0.58

REVEL

Benign

0.065

Sift

Benign

0.088

Sift4G

Benign

0.075

Polyphen

0.99

Vest4

0.14

MutPred

0.14

Loss of helix (P = 0.1299)

MVP

0.35

MPC

0.069

ClinPred

0.16

GERP RS

2.9

Varity_R

0.021

gMVP

0.13

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.23

Position offset: -7

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over