rs17743658

chr18-50950080-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002396.5(ME2):c.*2896G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,196 control chromosomes in the GnomAD database, including 3,918 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 0.20 (3918 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ME2 NM_002396.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330

Genes affected

ME2 (HGNC:6984): (malic enzyme 2) This gene encodes a mitochondrial NAD-dependent malic enzyme, a homotetrameric protein, that catalyzes the oxidative decarboxylation of malate to pyruvate. It had previously been weakly linked to a syndrome known as Friedreich ataxia that has since been shown to be the result of mutation in a completely different gene. Certain single-nucleotide polymorphism haplotypes of this gene have been shown to increase the risk for idiopathic generalized epilepsy. Alternatively spliced transcript variants encoding different isoforms found for this gene. [provided by RefSeq, Dec 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ME2	NM_002396.5	c.*2896G>A		3_prime_UTR_variant	16/16	ENST00000321341.11
ME2	NM_001168335.2	c.*3041G>A		3_prime_UTR_variant	14/14
ME2	NR_174094.1	n.4783G>A		non_coding_transcript_exon_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ME2	ENST00000321341.11	c.*2896G>A		3_prime_UTR_variant	16/16	1	NM_002396.5	P1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31008 AN: 152078 Hom.: 3917 Cov.: 32

Gnomad AFR AF: 0.0538

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.229

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.204 AC: 31006 AN: 152196 Hom.: 3918 Cov.: 32 AF XY: 0.205 AC XY: 15265 AN XY: 74388

Gnomad4 AFR AF: 0.0536

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.235

Alfa AF: 0.258 Hom.: 7147

Bravo AF: 0.191

Asia WGS AF: 0.252 AC: 876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.87
Dann	Benign	0.38

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: rs17743658; hg19: chr18-48476450;