chr11-57389932-A-G

Variant names:

• chr11-57389932-A-G
• rs490358
• NM_002728.6:c.13T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.710
• Publications: 29 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 -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 rank	MANE	Protein	UniProt
PRG2	NM_002728.6	c.13T>C	p.Leu5Leu	synonymous_variant	Exon 2 of 6	ENST00000311862.10	NP_002719.3
PRG2	NM_001302926.2	c.13T>C	p.Leu5Leu	synonymous_variant	Exon 2 of 6		NP_001289855.1
PRG2	NM_001302927.2	c.13T>C	p.Leu5Leu	synonymous_variant	Exon 2 of 6		NP_001289856.1
PRG2	NM_001243245.3	c.13T>C	p.Leu5Leu	synonymous_variant	Exon 2 of 6		NP_001230174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRG2	ENST00000311862.10	c.13T>C	p.Leu5Leu	synonymous_variant	Exon 2 of 6	1	NM_002728.6	ENSP00000312134.5
ENSG00000254979	ENST00000529411.1	c.328T>C	p.Leu110Leu	synonymous_variant	Exon 3 of 4	4		ENSP00000431536.1

Frequencies

GnomAD3 genomes AF: 0.718 AC: 109106 AN: 152002 Hom.: 39470 Cov.: 32

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

GnomAD2 exomes AF: 0.763 AC: 190630 AN: 249732 AF XY: 0.764

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 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.: 46 AF XY: 0.741 AC XY: 537843 AN XY: 725736

African (AFR) AF: 0.633 AC: 21130 AN: 33382

American (AMR) AF: 0.879 AC: 39061 AN: 44440

Ashkenazi Jewish (ASJ) AF: 0.772 AC: 20139 AN: 26084

East Asian (EAS) AF: 0.719 AC: 28539 AN: 39672

South Asian (SAS) AF: 0.821 AC: 70534 AN: 85962

European-Finnish (FIN) AF: 0.755 AC: 40115 AN: 53158

Middle Eastern (MID) AF: 0.770 AC: 4436 AN: 5760

European-Non Finnish (NFE) AF: 0.728 AC: 808233 AN: 1109942

Other (OTH) AF: 0.751 AC: 45281 AN: 60268

GnomAD4 genome AF: 0.718 AC: 109175 AN: 152120 Hom.: 39487 Cov.: 32 AF XY: 0.722 AC XY: 53712 AN XY: 74374

African (AFR) AF: 0.631 AC: 26180 AN: 41474

American (AMR) AF: 0.821 AC: 12564 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 2700 AN: 3472

East Asian (EAS) AF: 0.775 AC: 4006 AN: 5172

South Asian (SAS) AF: 0.831 AC: 4013 AN: 4828

European-Finnish (FIN) AF: 0.756 AC: 8000 AN: 10584

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.727 AC: 49383 AN: 67972

Other (OTH) AF: 0.722 AC: 1527 AN: 2116

Alfa AF: 0.730 Hom.: 77823

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
PhyloP100		0.71
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: rs490358; hg19: chr11-57157405; COSMIC: COSV108142786;