rs3741089

chr11-57388965-A-Gchr11-57388965-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

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]

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	UniProt
PRG2	NM_002728.6	c.366+45T>C		intron_variant		ENST00000311862.10
PRG2	NM_001243245.3	c.333+78T>C		intron_variant
PRG2	NM_001302926.2	c.366+45T>C		intron_variant
PRG2	NM_001302927.2	c.366+45T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRG2	ENST00000311862.10	c.366+45T>C		intron_variant		1	NM_002728.6	P1
PRG2	ENST00000525955.1	c.366+45T>C		intron_variant		2		P1
PRG2	ENST00000533605.5	c.333+78T>C		intron_variant		5
PRG2	ENST00000530105.1	n.457T>C		non_coding_transcript_exon_variant	3/5	5

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56695 AN: 151820 Hom.: 11192 Cov.: 31

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

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.: 32 AF XY: 0.432 AC XY: 307018 AN XY: 710830

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.: 31 AF XY: 0.369 AC XY: 27378 AN XY: 74264

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

Other links and lift over

dbSNP: rs3741089; hg19: chr11-57156438; COSMIC: COSV61293663; COSMIC: COSV61293663;