11-57389932-A-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002728.6(PRG2):​c.13T>A​(p.Leu5Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRG2 NM_002728.6 missense
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2439737).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRG2	NM_002728.6	c.13T>A	p.Leu5Ile	missense_variant	Exon 2 of 6	ENST00000311862.10	NP_002719.3
PRG2	NM_001302926.2	c.13T>A	p.Leu5Ile	missense_variant	Exon 2 of 6		NP_001289855.1
PRG2	NM_001302927.2	c.13T>A	p.Leu5Ile	missense_variant	Exon 2 of 6		NP_001289856.1
PRG2	NM_001243245.3	c.13T>A	p.Leu5Ile	missense_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>A	p.Leu5Ile	missense_variant	Exon 2 of 6	1	NM_002728.6	ENSP00000312134.5
ENSG00000254979	ENST00000529411.1	c.328T>A	p.Leu110Ile	missense_variant	Exon 3 of 4	4		ENSP00000431536.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1460082 Hom.: 0 Cov.: 46 AF XY: 0.00 AC XY: 0 AN XY: 726440

African (AFR) AF: 0.00 AC: 0 AN: 33430

American (AMR) AF: 0.00 AC: 0 AN: 44472

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86062

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53218

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110994

Other (OTH) AF: 0.00 AC: 0 AN: 60334

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.38	T;.;T;.
Eigen	Benign	-0.0087
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.65	.;T;T;T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Uncertain	0.18	D
MutationAssessor	Uncertain	2.3	M;M;M;.
PhyloP100		0.71
PROVEAN	Benign	-1.4	N;N;N;N
REVEL	Benign	0.072
Sift	Benign	0.030	D;D;D;T
Sift4G	Uncertain	0.015	D;D;D;T
Polyphen		1.0	D;.;D;.
Vest4		0.30
MutPred		0.36		Gain of catalytic residue at L5 (P = 0.0151);Gain of catalytic residue at L5 (P = 0.0151);Gain of catalytic residue at L5 (P = 0.0151);.;
MVP		0.75
MPC		0.050
ClinPred		0.53	D
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.11
gMVP		0.32
Mutation Taster		=99/1	polymorphism

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;