11-57389208-T-C

Position:

• chr11-57389208-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002728.6(PRG2):​c.168A>G​(p.Glu56Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00335 in 1,614,172 control chromosomes in the GnomAD database, including 152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (87 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (65 hom.)
• Consequence: PRG2 NM_002728.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.507

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

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 11-57389208-T-C is Benign according to our data. Variant chr11-57389208-T-C is described in ClinVar as [Benign]. Clinvar id is 789621.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.507 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRG2	NM_002728.6	c.168A>G	p.Glu56Glu	synonymous_variant	3/6	ENST00000311862.10	NP_002719.3
PRG2	NM_001302926.2	c.168A>G	p.Glu56Glu	synonymous_variant	3/6		NP_001289855.1
PRG2	NM_001302927.2	c.168A>G	p.Glu56Glu	synonymous_variant	3/6		NP_001289856.1
PRG2	NM_001243245.3	c.168A>G	p.Glu56Glu	synonymous_variant	3/6		NP_001230174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRG2	ENST00000311862.10	c.168A>G	p.Glu56Glu	synonymous_variant	3/6	1	NM_002728.6	ENSP00000312134.5
ENSG00000254979	ENST00000529411.1	c.483A>G	p.Glu161Glu	synonymous_variant	4/4	4		ENSP00000431536.1

Frequencies

GnomAD3 genomes AF: 0.0181 AC: 2754 AN: 152162 Hom.: 86 Cov.: 32

Gnomad AFR AF: 0.0640

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00438

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.0144

GnomAD3 exomes AF: 0.00448 AC: 1127 AN: 251482 Hom.: 26 AF XY: 0.00306 AC XY: 416 AN XY: 135916

Gnomad AFR exome AF: 0.0641

Gnomad AMR exome AF: 0.00205

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00181 AC: 2653 AN: 1461892 Hom.: 65 Cov.: 33 AF XY: 0.00158 AC XY: 1147 AN XY: 727248

Gnomad4 AFR exome AF: 0.0686

Gnomad4 AMR exome AF: 0.00253

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000207

Gnomad4 OTH exome AF: 0.00334

GnomAD4 genome AF: 0.0181 AC: 2759 AN: 152280 Hom.: 87 Cov.: 32 AF XY: 0.0175 AC XY: 1304 AN XY: 74456

Gnomad4 AFR AF: 0.0639

Gnomad4 AMR AF: 0.00438

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.00839 Hom.: 14

Bravo AF: 0.0207

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 30, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.79
DANN	Benign	0.47
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs77900153; hg19: chr11-57156681;