4-139704084-C-A

Position:

• chr4-139704084-C-A

Variant summary

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

The NM_002413.5(MGST2):​c.380C>A​(p.Ala127Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MGST2 NM_002413.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.786

Genes affected

MGST2 (HGNC:7063): (microsomal glutathione S-transferase 2) The MAPEG (Membrane Associated Proteins in Eicosanoid and Glutathione metabolism) family consists of six human proteins, several of which are involved in the production of leukotrienes and prostaglandin E, important mediators of inflammation. This gene encodes a protein which catalyzes the conjugation of leukotriene A4 and reduced glutathione to produce leukotriene C4. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene. [provided by RefSeq, Feb 2011]

MGST2 (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/exons	MANE	Protein	UniProt
MGST2	NM_002413.5	c.380C>A	p.Ala127Glu	missense_variant	5/5	ENST00000265498.6	NP_002404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGST2	ENST00000265498.6	c.380C>A	p.Ala127Glu	missense_variant	5/5	1	NM_002413.5	ENSP00000265498.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 26, 2024

The c.380C>A (p.A127E) alteration is located in exon 5 (coding exon 5) of the MGST2 gene. This alteration results from a C to A substitution at nucleotide position 380, causing the alanine (A) at amino acid position 127 to be replaced by a glutamic acid (E). 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	Pathogenic	0.70
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.28	T;T
Eigen	Benign	0.081
Eigen_PC	Benign	0.051
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.76	.;T
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.5	D;.
REVEL	Uncertain	0.46
Sift	Benign	0.074	T;.
Sift4G	Benign	0.15	T;T
Polyphen		0.94	P;P
Vest4		0.48
MutPred		0.68		Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);
MVP		0.77
MPC		0.19
ClinPred		0.80	D
GERP RS		4.2
Varity_R		0.23
gMVP		0.74

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-140625238;