10-104299210-A-G

Position:

• chr10-104299210-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_183239.2(GSTO2):​c.658A>G​(p.Lys220Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GSTO2 NM_183239.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.782

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06704554).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTO2	NM_183239.2	c.658A>G	p.Lys220Glu	missense_variant	7/7	ENST00000338595.7	NP_899062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTO2	ENST00000338595.7	c.658A>G	p.Lys220Glu	missense_variant	7/7	1	NM_183239.2	ENSP00000345023	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 29, 2022

The c.658A>G (p.K220E) alteration is located in exon 7 (coding exon 6) of the GSTO2 gene. This alteration results from a A to G substitution at nucleotide position 658, causing the lysine (K) at amino acid position 220 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	15
DANN	Benign	0.52
DEOGEN2	Benign	0.028	.;T;.
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.14	T;T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.067	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	.;N;.
MutationTaster	Benign	1.0	D;N;N;N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.010	N;N;N
REVEL	Benign	0.095
Sift	Benign	0.73	T;T;T
Sift4G	Benign	0.88	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.35
MutPred		0.47		.;Loss of ubiquitination at K220 (P = 0.0233);.;
MVP		0.34
MPC		0.11
ClinPred		0.050	T
GERP RS		3.4
Varity_R		0.11
gMVP		0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs2013181417; hg19: chr10-106058968;