rs11076256

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002080.4(GOT2):c.562G>A(p.Gly188Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0736 in 1,596,714 control chromosomes in the GnomAD database, including 4,759 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 299 hom., cov: 33)

Exomes 𝑓: 0.075 ( 4460 hom. )

Consequence

GOT2
NM_002080.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 6.04

Publications

33 publications found

Variant links:

Genes affected

GOT2 (HGNC:4433): (glutamic-oxaloacetic transaminase 2) Glutamic-oxaloacetic transaminase is a pyridoxal phosphate-dependent enzyme which exists in cytoplasmic and inner-membrane mitochondrial forms, GOT1 and GOT2, respectively. GOT plays a role in amino acid metabolism and the urea and tricarboxylic acid cycles. The two enzymes are homodimeric and show close homology. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]

GOT2 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy, 82
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

GOT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035402477).

BP6

Variant 16-58718562-C-T is Benign according to our data. Variant chr16-58718562-C-T is described in ClinVar as Benign. ClinVar VariationId is 1555382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOT2	NM_002080.4 link	c.562G>A	p.Gly188Ser	missense_variant	Exon 5 of 10	ENST00000245206.10	NP_002071.2	P00505-1
GOT2	NM_001286220.2 link	c.433G>A	p.Gly145Ser	missense_variant	Exon 4 of 9		NP_001273149.1	P00505-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOT2	ENST00000245206.10 link	c.562G>A	p.Gly188Ser	missense_variant	Exon 5 of 10	1	NM_002080.4	ENSP00000245206.5		P00505-1

Frequencies

GnomAD3 genomes

AF:

0.0572

AC:

8704

AN:

152120

Hom.:

299

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0307

Gnomad AMI

AF:

0.0198

Gnomad AMR

AF:

0.0410

Gnomad ASJ

AF:

0.0314

Gnomad EAS

AF:

0.00713

Gnomad SAS

AF:

0.0873

Gnomad FIN

AF:

0.0586

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0799

Gnomad OTH

AF:

0.0689

GnomAD2 exomes

AF:

0.0612

AC:

14703

AN:

240202

AF XY:

0.0647

show subpopulations

Gnomad AFR exome

AF:

0.0305

Gnomad AMR exome

AF:

0.0261

Gnomad ASJ exome

AF:

0.0350

Gnomad EAS exome

AF:

0.00679

Gnomad FIN exome

AF:

0.0581

Gnomad NFE exome

AF:

0.0799

Gnomad OTH exome

AF:

0.0549

GnomAD4 exome

AF:

0.0754

AC:

108880

AN:

1444476

Hom.:

4460

Cov.:

AF XY:

0.0757

AC XY:

54275

AN XY:

716772

show subpopulations

African (AFR)

AF:

0.0277

AC:

904

AN:

32626

American (AMR)

AF:

0.0276

AC:

1134

AN:

41054

Ashkenazi Jewish (ASJ)

AF:

0.0353

AC:

902

AN:

25560

East Asian (EAS)

AF:

0.00603

AC:

238

AN:

39476

South Asian (SAS)

AF:

0.0898

AC:

7483

AN:

83360

European-Finnish (FIN)

AF:

0.0582

AC:

3101

AN:

53278

Middle Eastern (MID)

AF:

0.0466

AC:

264

AN:

5668

European-Non Finnish (NFE)

AF:

0.0825

AC:

91061

AN:

1103826

Other (OTH)

AF:

0.0636

AC:

3793

AN:

59628

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

4540

9081

13621

18162

22702

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3380

6760

10140

13520

16900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0571

AC:

8695

AN:

152238

Hom.:

299

Cov.:

AF XY:

0.0563

AC XY:

4187

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0307

AC:

1275

AN:

41546

American (AMR)

AF:

0.0409

AC:

626

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0314

AC:

109

AN:

3470

East Asian (EAS)

AF:

0.00696

AC:

AN:

5176

South Asian (SAS)

AF:

0.0861

AC:

416

AN:

4832

European-Finnish (FIN)

AF:

0.0586

AC:

621

AN:

10596

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0799

AC:

5436

AN:

68012

Other (OTH)

AF:

0.0682

AC:

144

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

409

818

1226

1635

2044

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

220

330

440

550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0677

Hom.:

762

Bravo

AF:

0.0534

TwinsUK

AF:

0.0850

AC:

315

ALSPAC

AF:

0.0854

AC:

329

ESP6500AA

AF:

0.0316

AC:

139

ESP6500EA

AF:

0.0791

AC:

680

ExAC

AF:

0.0633

AC:

7684

Asia WGS

AF:

0.0520

AC:

180

AN:

3478

EpiCase

AF:

0.0751

EpiControl

AF:

0.0765

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

GOT2-related disorder

Benign:1

Mar 14, 2024

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

D;.

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.83

T;T

MetaRNN

Benign

0.0035

T;T

MetaSVM

Benign

-0.59

MutationAssessor

Uncertain

2.1

M;.

PhyloP100

6.0

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-5.3

D;D

REVEL

Uncertain

0.42

Sift

Benign

0.043

D;D

Sift4G

Benign

0.097

T;T

Polyphen

0.73

P;.

Vest4

0.052

MPC

0.67

ClinPred

0.025

GERP RS

5.7

Varity_R

0.77

gMVP

0.68

Mutation Taster

=78/22

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over