rs12600277

Variant names:

• chr16-58725428-C-G
• rs12600277
• NM_002080.4:c.90-1526G>C

Variant summary

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

The NM_002080.4(GOT2):​c.90-1526G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0957 in 152,106 control chromosomes in the GnomAD database, including 1,486 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 0.096 (1486 hom., cov: 32)
• Consequence: GOT2 NM_002080.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440
• Publications: 9 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOT2	NM_002080.4	c.90-1526G>C		intron_variant	Intron 1 of 9	ENST00000245206.10	NP_002071.2
GOT2	NM_001286220.2	c.90-1526G>C		intron_variant	Intron 1 of 8		NP_001273149.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOT2	ENST00000245206.10	c.90-1526G>C		intron_variant	Intron 1 of 9	1	NM_002080.4	ENSP00000245206.5

Frequencies

GnomAD3 genomes AF: 0.0956 AC: 14525 AN: 151988 Hom.: 1481 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.00923

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.0704

Gnomad FIN AF: 0.0349

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0162

Gnomad OTH AF: 0.0918

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0957 AC: 14559 AN: 152106 Hom.: 1486 Cov.: 32 AF XY: 0.101 AC XY: 7528 AN XY: 74366

African (AFR) AF: 0.168 AC: 6970 AN: 41478

American (AMR) AF: 0.241 AC: 3682 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00923 AC: 32 AN: 3466

East Asian (EAS) AF: 0.358 AC: 1848 AN: 5160

South Asian (SAS) AF: 0.0703 AC: 339 AN: 4824

European-Finnish (FIN) AF: 0.0349 AC: 370 AN: 10600

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0162 AC: 1102 AN: 67998

Other (OTH) AF: 0.0956 AC: 202 AN: 2114

Alfa AF: 0.0601 Hom.: 116

Bravo AF: 0.117

Asia WGS AF: 0.225 AC: 783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.62
PhyloP100		-0.044
Mutation Taster		=100/0	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: rs12600277; hg19: chr16-58759332;