11-57389141-C-T

Variant names:

• chr11-57389141-C-T
• NM_002728.6:c.235G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002728.6(PRG2):​c.235G>A​(p.Val79Met) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRG2 NM_002728.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.448

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRG2	NM_002728.6	c.235G>A	p.Val79Met	missense_variant	Exon 3 of 6	ENST00000311862.10	NP_002719.3
PRG2	NM_001302926.2	c.235G>A	p.Val79Met	missense_variant	Exon 3 of 6		NP_001289855.1
PRG2	NM_001302927.2	c.235G>A	p.Val79Met	missense_variant	Exon 3 of 6		NP_001289856.1
PRG2	NM_001243245.3	c.235G>A	p.Val79Met	missense_variant	Exon 3 of 6		NP_001230174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRG2	ENST00000311862.10	c.235G>A	p.Val79Met	missense_variant	Exon 3 of 6	1	NM_002728.6	ENSP00000312134.5
ENSG00000254979	ENST00000529411.1	c.550G>A	p.Val184Met	missense_variant	Exon 4 of 4	4		ENSP00000431536.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.235G>A (p.V79M) alteration is located in exon 3 (coding exon 2) of the PRG2 gene. This alteration results from a G to A substitution at nucleotide position 235, causing the valine (V) at amino acid position 79 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;.;T;.
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.50	.;T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.091	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N;N;.
PROVEAN	Benign	-0.58	N;N;N;N
REVEL	Benign	0.065
Sift	Benign	0.088	T;T;T;D
Sift4G	Benign	0.075	T;T;T;T
Polyphen		0.99	D;.;D;.
Vest4		0.14
MutPred		0.14		Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);.;
MVP		0.35
MPC		0.069
ClinPred		0.16	T
GERP RS		2.9
Varity_R		0.021
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.23		Position offset: -7

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-57156614;