11-57388965-A-G

Variant names:

• chr11-57388965-A-G
• rs3741089
• NM_002728.6:c.366+45T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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]

ENSG00000254979 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRG2	NM_002728.6	MANE Select	c.366+45T>C		intron	N/A	NP_002719.3
	PRG2	NM_001302926.2		c.366+45T>C		intron	N/A	NP_001289855.1	P13727-1
	PRG2	NM_001302927.2		c.366+45T>C		intron	N/A	NP_001289856.1	P13727-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRG2	ENST00000311862.10	TSL:1 MANE Select	c.366+45T>C		intron	N/A	ENSP00000312134.5	P13727-1
	PRG2	ENST00000525955.1	TSL:2	c.366+45T>C		intron	N/A	ENSP00000433016.1	P13727-1
	PRG2	ENST00000886024.1		c.366+45T>C		intron	N/A	ENSP00000556083.1

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

GnomAD2 exomes AF: 0.365 AC: 84115 AN: 230746 AF XY: 0.372

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 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

African (AFR) AF: 0.266 AC: 8780 AN: 33024

American (AMR) AF: 0.197 AC: 8599 AN: 43632

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 8952 AN: 24394

East Asian (EAS) AF: 0.289 AC: 11403 AN: 39520

South Asian (SAS) AF: 0.307 AC: 25176 AN: 82010

European-Finnish (FIN) AF: 0.409 AC: 19655 AN: 48100

Middle Eastern (MID) AF: 0.340 AC: 1715 AN: 5040

European-Non Finnish (NFE) AF: 0.468 AC: 513829 AN: 1098426

Other (OTH) AF: 0.398 AC: 23602 AN: 59306

GnomAD4 genome AF: 0.373 AC: 56724 AN: 151940 Hom.: 11192 Cov.: 31 AF XY: 0.369 AC XY: 27378 AN XY: 74264

African (AFR) AF: 0.280 AC: 11587 AN: 41428

American (AMR) AF: 0.278 AC: 4244 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1244 AN: 3464

East Asian (EAS) AF: 0.247 AC: 1272 AN: 5146

South Asian (SAS) AF: 0.295 AC: 1418 AN: 4814

European-Finnish (FIN) AF: 0.400 AC: 4213 AN: 10542

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.463 AC: 31446 AN: 67972

Other (OTH) AF: 0.377 AC: 792 AN: 2102

Alfa AF: 0.426 Hom.: 31438

Bravo AF: 0.360

Asia WGS AF: 0.232 AC: 809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.67
DANN	Benign	0.60
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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