Variant 11-57389932-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002728.6(PRG2):c.13T>C(p.Leu5Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 1,610,788 control chromosomes in the GnomAD database, including 438,591 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 0.72 ( 39487 hom., cov: 32)

Exomes 𝑓: 0.74 ( 399104 hom. )

Consequence

PRG2
NM_002728.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.710

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 made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP7

Synonymous conserved (PhyloP=0.71 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRG2	NM_002728.6 linkuse as main transcript	c.13T>C	p.Leu5Leu	synonymous_variant	2/6	ENST00000311862.10	NP_002719.3	P13727-1
PRG2	NM_001302926.2 linkuse as main transcript	c.13T>C	p.Leu5Leu	synonymous_variant	2/6		NP_001289855.1	P13727-1
PRG2	NM_001302927.2 linkuse as main transcript	c.13T>C	p.Leu5Leu	synonymous_variant	2/6		NP_001289856.1	P13727-1
PRG2	NM_001243245.3 linkuse as main transcript	c.13T>C	p.Leu5Leu	synonymous_variant	2/6		NP_001230174.1	P13727-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRG2	ENST00000311862.10 linkuse as main transcript	c.13T>C	p.Leu5Leu	synonymous_variant	2/6	1	NM_002728.6	ENSP00000312134.5		P13727-1
ENSG00000254979	ENST00000529411.1 linkuse as main transcript	c.328T>C	p.Leu110Leu	synonymous_variant	3/4	4		ENSP00000431536.1		H0YCG3

Frequencies

GnomAD3 genomes

AF:

0.718

AC:

109106

AN:

152002

Hom.:

39470

Cov.:

show subpopulations

Gnomad AFR

AF:

0.632

Gnomad AMI

AF:

0.635

Gnomad AMR

AF:

0.821

Gnomad ASJ

AF:

0.778

Gnomad EAS

AF:

0.774

Gnomad SAS

AF:

0.831

Gnomad FIN

AF:

0.756

Gnomad MID

AF:

0.744

Gnomad NFE

AF:

0.727

Gnomad OTH

AF:

0.720

GnomAD3 exomes

AF:

0.763

AC:

190630

AN:

249732

Hom.:

73397

AF XY:

0.764

AC XY:

103283

AN XY:

135216

show subpopulations

Gnomad AFR exome

AF:

0.635

Gnomad AMR exome

AF:

0.883

Gnomad ASJ exome

AF:

0.774

Gnomad EAS exome

AF:

0.780

Gnomad SAS exome

AF:

0.822

Gnomad FIN exome

AF:

0.750

Gnomad NFE exome

AF:

0.728

Gnomad OTH exome

AF:

0.776

GnomAD4 exome

AF:

0.739

AC:

1077468

AN:

1458668

Hom.:

399104

Cov.:

AF XY:

0.741

AC XY:

537843

AN XY:

725736

show subpopulations

Gnomad4 AFR exome

AF:

0.633

Gnomad4 AMR exome

AF:

0.879

Gnomad4 ASJ exome

AF:

0.772

Gnomad4 EAS exome

AF:

0.719

Gnomad4 SAS exome

AF:

0.821

Gnomad4 FIN exome

AF:

0.755

Gnomad4 NFE exome

AF:

0.728

Gnomad4 OTH exome

AF:

0.751

GnomAD4 genome

AF:

0.718

AC:

109175

AN:

152120

Hom.:

39487

Cov.:

AF XY:

0.722

AC XY:

53712

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.631

Gnomad4 AMR

AF:

0.821

Gnomad4 ASJ

AF:

0.778

Gnomad4 EAS

AF:

0.775

Gnomad4 SAS

AF:

0.831

Gnomad4 FIN

AF:

0.756

Gnomad4 NFE

AF:

0.727

Gnomad4 OTH

AF:

0.722

Alfa

AF:

0.731

Hom.:

63711

Bravo

AF:

0.719

Asia WGS

AF:

0.805

AC:

2803

AN:

3478

EpiCase

AF:

0.732

EpiControl

AF:

0.724

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

6.3

DANN

Benign

0.84

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over