rs2234951

Positions:

• chr6-52752940-G-A
• chr6-52752940-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000846.5(GSTA2):​c.328C>T​(p.Pro110Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0477 in 1,613,666 control chromosomes in the GnomAD database, including 2,655 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.039 (220 hom., cov: 32)
  • Exomes 𝑓: 0.049 (2435 hom.)
• Consequence: GSTA2 NM_000846.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.113

Genes affected

GSTA2 (HGNC:4627): (glutathione S-transferase alpha 2) Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. These enzymes function in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding these enzymes are known to be highly polymorphic. These genetic variations can change an individual's susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of some drugs. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-tranferase belonging to the alpha class. The alpha class genes, located in a cluster mapped to chromosome 6, are the most abundantly expressed glutathione S-transferases in liver. In addition to metabolizing bilirubin and certain anti-cancer drugs in the liver, the alpha class of these enzymes exhibit glutathione peroxidase activity thereby protecting the cells from reactive oxygen species and the products of peroxidation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTA2	NM_000846.5	c.328C>T	p.Pro110Ser	missense_variant	5/7	ENST00000493422.3	NP_000837.3
GSTA2	XM_047418684.1	c.328C>T	p.Pro110Ser	missense_variant	6/8		XP_047274640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTA2	ENST00000493422.3	c.328C>T	p.Pro110Ser	missense_variant	5/7	1	NM_000846.5	ENSP00000420168	P1

Frequencies

GnomAD3 genomes AF: 0.0393 AC: 5977 AN: 152096 Hom.: 221 Cov.: 32

Gnomad AFR AF: 0.00715

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0251

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0397

Gnomad OTH AF: 0.0383

GnomAD3 exomes AF: 0.0565 AC: 14200 AN: 251234 Hom.: 690 AF XY: 0.0616 AC XY: 8366 AN XY: 135768

Gnomad AFR exome AF: 0.00627

Gnomad AMR exome AF: 0.0181

Gnomad ASJ exome AF: 0.0215

Gnomad EAS exome AF: 0.123

Gnomad SAS exome AF: 0.130

Gnomad FIN exome AF: 0.108

Gnomad NFE exome AF: 0.0384

Gnomad OTH exome AF: 0.0491

GnomAD4 exome AF: 0.0486 AC: 71063 AN: 1461452 Hom.: 2435 Cov.: 32 AF XY: 0.0508 AC XY: 36952 AN XY: 727036

Gnomad4 AFR exome AF: 0.00586

Gnomad4 AMR exome AF: 0.0191

Gnomad4 ASJ exome AF: 0.0228

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.127

Gnomad4 FIN exome AF: 0.108

Gnomad4 NFE exome AF: 0.0400

Gnomad4 OTH exome AF: 0.0510

GnomAD4 genome AF: 0.0393 AC: 5977 AN: 152214 Hom.: 220 Cov.: 32 AF XY: 0.0444 AC XY: 3302 AN XY: 74412

Gnomad4 AFR AF: 0.00713

Gnomad4 AMR AF: 0.0251

Gnomad4 ASJ AF: 0.0248

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.0397

Gnomad4 OTH AF: 0.0379

Alfa AF: 0.0389 Hom.: 407

Bravo AF: 0.0288

TwinsUK AF: 0.0407 AC: 151

ALSPAC AF: 0.0402 AC: 155

ESP6500AA AF: 0.00772 AC: 34

ESP6500EA AF: 0.0347 AC: 298

ExAC AF: 0.0569 AC: 6904

Asia WGS AF: 0.129 AC: 448 AN: 3478

EpiCase AF: 0.0357

EpiControl AF: 0.0372

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.12
Sift	Benign	0.091	T
Sift4G	Benign	0.11	T
Polyphen		0.0050	B
Vest4		0.066
MPC		0.020
ClinPred		0.018	T
GERP RS		1.3
Varity_R		0.27
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.22		Position offset: -8

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

Publications

LitVar

Other links and lift over

dbSNP: rs2234951; hg19: chr6-52617738; COSMIC: COSV72414589;