Variant 4-139703502-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_002413.5(MGST2):c.277T>C(p.Tyr93His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00834 in 1,614,028 control chromosomes in the GnomAD database, including 108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0055 ( 9 hom., cov: 31)

Exomes 𝑓: 0.0086 ( 99 hom. )

Consequence

MGST2
NM_002413.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.85

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007955819).

BP6

Variant 4-139703502-T-C is Benign according to our data. Variant chr4-139703502-T-C is described in ClinVar as [Benign]. Clinvar id is 790448.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00864 (12626/1461750) while in subpopulation SAS AF= 0.0188 (1618/86256). AF 95% confidence interval is 0.018. There are 99 homozygotes in gnomad4_exome. There are 6570 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGST2	NM_002413.5 linkuse as main transcript	c.277T>C	p.Tyr93His	missense_variant	4/5	ENST00000265498.6	NP_002404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGST2	ENST00000265498.6 linkuse as main transcript	c.277T>C	p.Tyr93His	missense_variant	4/5	1	NM_002413.5	ENSP00000265498	P1	Q99735-1

Frequencies

GnomAD3 genomes

AF:

0.00553

AC:

842

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0166

Gnomad FIN

AF:

0.00575

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00836

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00739

AC:

1857

AN:

251402

Hom.:

AF XY:

0.00820

AC XY:

1114

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00220

Gnomad ASJ exome

AF:

0.00853

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0187

Gnomad FIN exome

AF:

0.00564

Gnomad NFE exome

AF:

0.00830

Gnomad OTH exome

AF:

0.00603

GnomAD4 exome

AF:

0.00864

AC:

12626

AN:

1461750

Hom.:

Cov.:

AF XY:

0.00903

AC XY:

6570

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.00235

Gnomad4 ASJ exome

AF:

0.00911

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0188

Gnomad4 FIN exome

AF:

0.00509

Gnomad4 NFE exome

AF:

0.00883

Gnomad4 OTH exome

AF:

0.00831

GnomAD4 genome

AF:

0.00552

AC:

840

AN:

152278

Hom.:

Cov.:

AF XY:

0.00534

AC XY:

398

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0162

Gnomad4 FIN

AF:

0.00575

Gnomad4 NFE

AF:

0.00836

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00790

Hom.:

Bravo

AF:

0.00481

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.00986

AC:

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.00837

AC:

ExAC

AF:

0.00821

AC:

997

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.00829

EpiControl

AF:

0.00735

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.88

BayesDel_addAF

Uncertain

0.090

BayesDel_noAF

Uncertain

0.10

CADD

Uncertain

DANN

Uncertain

0.99

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.33

MetaRNN

Benign

0.0080

MetaSVM

Uncertain

0.038

MutationTaster

Benign

1.0

D;N

PROVEAN

Benign

-1.4

REVEL

Benign

0.095

Sift

Benign

0.061

Sift4G

Benign

0.22

Vest4

0.39

MVP

0.72

ClinPred

0.040

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over