Variant rs3741089 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002728.6(PRG2):c.366+45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 1,585,392 control chromosomes in the GnomAD database, including 150,040 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 0.37 ( 11192 hom., cov: 31)

Exomes 𝑓: 0.43 ( 138848 hom. )

Consequence

PRG2
NM_002728.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.74

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
PRG2	NM_002728.6 linkuse as main transcript	c.366+45T>C	intron_variant	ENST00000311862.10	NP_002719.3
PRG2	NM_001243245.3 linkuse as main transcript	c.333+78T>C	intron_variant		NP_001230174.1
PRG2	NM_001302926.2 linkuse as main transcript	c.366+45T>C	intron_variant		NP_001289855.1
PRG2	NM_001302927.2 linkuse as main transcript	c.366+45T>C	intron_variant		NP_001289856.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRG2	ENST00000311862.10 linkuse as main transcript	c.366+45T>C	intron_variant		1	NM_002728.6	ENSP00000312134	P1	P13727-1
PRG2	ENST00000525955.1 linkuse as main transcript	c.366+45T>C	intron_variant		2		ENSP00000433016	P1	P13727-1
PRG2	ENST00000533605.5 linkuse as main transcript	c.333+78T>C	intron_variant		5		ENSP00000433231		P13727-2
PRG2	ENST00000530105.1 linkuse as main transcript	n.457T>C	non_coding_transcript_exon_variant	3/5	5

Frequencies

GnomAD3 genomes

AF:

0.373

AC:

56695

AN:

151820

Hom.:

11192

Cov.:

show subpopulations

Gnomad AFR

AF:

0.279

Gnomad AMI

AF:

0.444

Gnomad AMR

AF:

0.278

Gnomad ASJ

AF:

0.359

Gnomad EAS

AF:

0.247

Gnomad SAS

AF:

0.295

Gnomad FIN

AF:

0.400

Gnomad MID

AF:

0.363

Gnomad NFE

AF:

0.463

Gnomad OTH

AF:

0.381

GnomAD3 exomes

AF:

0.365

AC:

84115

AN:

230746

Hom.:

16783

AF XY:

0.372

AC XY:

46292

AN XY:

124288

show subpopulations

Gnomad AFR exome

AF:

0.276

Gnomad AMR exome

AF:

0.188

Gnomad ASJ exome

AF:

0.370

Gnomad EAS exome

AF:

0.249

Gnomad SAS exome

AF:

0.299

Gnomad FIN exome

AF:

0.412

Gnomad NFE exome

AF:

0.462

Gnomad OTH exome

AF:

0.380

GnomAD4 exome

AF:

0.434

AC:

621711

AN:

1433452

Hom.:

138848

Cov.:

AF XY:

0.432

AC XY:

307018

AN XY:

710830

show subpopulations

Gnomad4 AFR exome

AF:

0.266

Gnomad4 AMR exome

AF:

0.197

Gnomad4 ASJ exome

AF:

0.367

Gnomad4 EAS exome

AF:

0.289

Gnomad4 SAS exome

AF:

0.307

Gnomad4 FIN exome

AF:

0.409

Gnomad4 NFE exome

AF:

0.468

Gnomad4 OTH exome

AF:

0.398

GnomAD4 genome

AF:

0.373

AC:

56724

AN:

151940

Hom.:

11192

Cov.:

AF XY:

0.369

AC XY:

27378

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.280

Gnomad4 AMR

AF:

0.278

Gnomad4 ASJ

AF:

0.359

Gnomad4 EAS

AF:

0.247

Gnomad4 SAS

AF:

0.295

Gnomad4 FIN

AF:

0.400

Gnomad4 NFE

AF:

0.463

Gnomad4 OTH

AF:

0.377

Alfa

AF:

0.436

Hom.:

20146

Bravo

AF:

0.360

Asia WGS

AF:

0.232

AC:

809

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.67

DANN

Benign

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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