4-139703502-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.85

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]

ACMG classification

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 GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGST2	NM_002413.5	c.277T>C	p.Tyr93His	missense_variant	4/5	ENST00000265498.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGST2	ENST00000265498.6	c.277T>C	p.Tyr93His	missense_variant	4/5	1	NM_002413.5	P1

Frequencies

GnomAD3 genomes AF: 0.00553 AC: 842 AN: 152160 Hom.: 9 Cov.: 31

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.: 17 AF XY: 0.00820 AC XY: 1114 AN XY: 135890

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.: 99 Cov.: 31 AF XY: 0.00903 AC XY: 6570 AN XY: 727176

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.: 9 Cov.: 31 AF XY: 0.00534 AC XY: 398 AN XY: 74464

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.: 11

Bravo AF: 0.00481

TwinsUK AF: 0.00863 AC: 32

ALSPAC AF: 0.00986 AC: 38

ESP6500AA AF: 0.00295 AC: 13

ESP6500EA AF: 0.00837 AC: 72

ExAC AF: 0.00821 AC: 997

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.00829

EpiControl AF: 0.00735

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 23, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.090	D
BayesDel_noAF	Uncertain	0.10
Cadd	Uncertain	24
Dann	Uncertain	0.99
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.0080	T
MetaSVM	Uncertain	0.038	D
MutationTaster	Benign	1.0	D;N
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.095
Sift	Benign	0.061	T
Sift4G	Benign	0.22	T
Vest4		0.39
MVP		0.72
ClinPred		0.040	T
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

Other links and lift over

dbSNP: rs116372322; hg19: chr4-140624656; COSMIC: COSV99643690; COSMIC: COSV99643690;