rs2234951

Variant names:

• chr6-52752940-G-A
• rs2234951
• NM_000846.5:c.328C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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.

• 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
• Publications: 22 publications found

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]

ENSG00000301390 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GSTA2	NM_000846.5	c.328C>T	p.Pro110Ser	missense_variant	Exon 5 of 7	ENST00000493422.3	NP_000837.3
GSTA2	XM_047418684.1	c.328C>T	p.Pro110Ser	missense_variant	Exon 6 of 8		XP_047274640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTA2	ENST00000493422.3	c.328C>T	p.Pro110Ser	missense_variant	Exon 5 of 7	1	NM_000846.5	ENSP00000420168.1
ENSG00000301390	ENST00000778609.1	n.73-6669G>A		intron_variant	Intron 1 of 1

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

GnomAD2 exomes AF: 0.0565 AC: 14200 AN: 251234 AF XY: 0.0616

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 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

African (AFR) AF: 0.00586 AC: 196 AN: 33472

American (AMR) AF: 0.0191 AC: 852 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0228 AC: 595 AN: 26132

East Asian (EAS) AF: 0.125 AC: 4964 AN: 39676

South Asian (SAS) AF: 0.127 AC: 10965 AN: 86240

European-Finnish (FIN) AF: 0.108 AC: 5763 AN: 53400

Middle Eastern (MID) AF: 0.0351 AC: 202 AN: 5760

European-Non Finnish (NFE) AF: 0.0400 AC: 44445 AN: 1111668

Other (OTH) AF: 0.0510 AC: 3081 AN: 60384

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

African (AFR) AF: 0.00713 AC: 296 AN: 41522

American (AMR) AF: 0.0251 AC: 384 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0248 AC: 86 AN: 3470

East Asian (EAS) AF: 0.123 AC: 635 AN: 5174

South Asian (SAS) AF: 0.131 AC: 631 AN: 4812

European-Finnish (FIN) AF: 0.109 AC: 1153 AN: 10600

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0397 AC: 2699 AN: 68026

Other (OTH) AF: 0.0379 AC: 80 AN: 2112

Alfa AF: 0.0379 Hom.: 492

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
PhyloP100		0.11
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
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

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