chr11-57387805-C-T

Variant names:

• chr11-57387805-C-T
• rs149013013
• NM_002728.6:c.559G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002728.6(PRG2):​c.559G>A​(p.Ala187Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,439,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A187S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PRG2 NM_002728.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.89
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046226203).

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.559G>A	p.Ala187Thr	missense	Exon 5 of 6	NP_002719.3
	PRG2	NM_001302926.2		c.559G>A	p.Ala187Thr	missense	Exon 5 of 6	NP_001289855.1	P13727-1
	PRG2	NM_001302927.2		c.559G>A	p.Ala187Thr	missense	Exon 5 of 6	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.559G>A	p.Ala187Thr	missense	Exon 5 of 6	ENSP00000312134.5	P13727-1
	PRG2	ENST00000525955.1	TSL:2	c.559G>A	p.Ala187Thr	missense	Exon 5 of 6	ENSP00000433016.1	P13727-1
	PRG2	ENST00000886024.1		c.559G>A	p.Ala187Thr	missense	Exon 5 of 6	ENSP00000556083.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1439792 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 713788

African (AFR) AF: 0.00 AC: 0 AN: 33328

American (AMR) AF: 0.00 AC: 0 AN: 40576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25480

East Asian (EAS) AF: 0.00 AC: 0 AN: 39008

South Asian (SAS) AF: 0.00 AC: 0 AN: 82210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51748

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 9.07e-7 AC: 1 AN: 1102036

Other (OTH) AF: 0.00 AC: 0 AN: 59664

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.0030
DANN	Benign	0.74
DEOGEN2	Benign	0.13	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0092	N
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.99	L
PhyloP100		-6.9
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.025
Sift	Benign	0.46	T
Sift4G	Benign	0.48	T
Polyphen		0.15	B
Vest4		0.072
MutPred		0.35		Loss of MoRF binding (P = 0.106)
MVP		0.15
MPC		0.046
ClinPred		0.096	T
GERP RS		-9.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.20
gMVP		0.18
Mutation Taster		=96/4	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: rs149013013; hg19: chr11-57155278;