10-104279427-A-G

Variant names:

• chr10-104279427-A-G
• rs156697
• NM_183239.2:c.424A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_183239.2(GSTO2):​c.424A>G​(p.Asn142Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 1,612,916 control chromosomes in the GnomAD database, including 109,695 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.45 (17858 hom., cov: 31)
  • Exomes 𝑓: 0.35 (91837 hom.)
• Consequence: GSTO2 NM_183239.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.575
• Publications: 168 publications found

Genes affected

GSTO2 (HGNC:23064): (glutathione S-transferase omega 2) The protein encoded by this gene is an omega class glutathione S-transferase (GST). GSTs are involved in the metabolism of xenobiotics and carcinogens. Four transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.1534677E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTO2	NM_183239.2	c.424A>G	p.Asn142Asp	missense_variant	Exon 5 of 7	ENST00000338595.7	NP_899062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTO2	ENST00000338595.7	c.424A>G	p.Asn142Asp	missense_variant	Exon 5 of 7	1	NM_183239.2	ENSP00000345023.1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67758 AN: 151886 Hom.: 17810 Cov.: 31

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.428

GnomAD2 exomes AF: 0.348 AC: 87337 AN: 251258 AF XY: 0.344

Gnomad AFR exome AF: 0.749

Gnomad AMR exome AF: 0.239

Gnomad ASJ exome AF: 0.421

Gnomad EAS exome AF: 0.239

Gnomad FIN exome AF: 0.318

Gnomad NFE exome AF: 0.343

Gnomad OTH exome AF: 0.360

GnomAD4 exome AF: 0.347 AC: 506293 AN: 1460912 Hom.: 91837 Cov.: 35 AF XY: 0.345 AC XY: 250879 AN XY: 726796

African (AFR) AF: 0.757 AC: 25328 AN: 33468

American (AMR) AF: 0.248 AC: 11074 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 11199 AN: 26120

East Asian (EAS) AF: 0.258 AC: 10253 AN: 39686

South Asian (SAS) AF: 0.331 AC: 28548 AN: 86218

European-Finnish (FIN) AF: 0.318 AC: 17006 AN: 53406

Middle Eastern (MID) AF: 0.402 AC: 2312 AN: 5756

European-Non Finnish (NFE) AF: 0.341 AC: 378552 AN: 1111210

Other (OTH) AF: 0.365 AC: 22021 AN: 60354

GnomAD4 genome AF: 0.446 AC: 67860 AN: 152004 Hom.: 17858 Cov.: 31 AF XY: 0.439 AC XY: 32614 AN XY: 74316

African (AFR) AF: 0.741 AC: 30706 AN: 41452

American (AMR) AF: 0.327 AC: 4990 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1487 AN: 3470

East Asian (EAS) AF: 0.248 AC: 1282 AN: 5162

South Asian (SAS) AF: 0.333 AC: 1601 AN: 4808

European-Finnish (FIN) AF: 0.307 AC: 3250 AN: 10588

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23338 AN: 67940

Other (OTH) AF: 0.425 AC: 896 AN: 2106

Alfa AF: 0.380 Hom.: 48821

Bravo AF: 0.462

TwinsUK AF: 0.340 AC: 1260

ALSPAC AF: 0.347 AC: 1336

ESP6500AA AF: 0.743 AC: 3273

ESP6500EA AF: 0.341 AC: 2929

ExAC AF: 0.356 AC: 43214

Asia WGS AF: 0.339 AC: 1179 AN: 3478

EpiCase AF: 0.352

EpiControl AF: 0.358

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.6
DANN	Benign	0.30
DEOGEN2	Benign	0.027	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.00082	N
LIST_S2	Benign	0.058	T;T
MetaRNN	Benign	8.2e-7	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.3	N;.
PhyloP100		0.57
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.020	N;N
REVEL	Benign	0.046
Sift	Benign	0.61	T;T
Sift4G	Benign	0.87	T;T
Polyphen		0.0	B;.
Vest4		0.019
MPC		0.087
ClinPred		0.00030	T
GERP RS		4.0
Varity_R		0.44
gMVP		0.24
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs156697; hg19: chr10-106039185; COSMIC: COSV58537765;