rs12277

Positions:

• chr18-50947383-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.*199G>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 0.641 in 559,414 control chromosomes in the GnomAD database, including 116,060 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 0.66 (33215 hom., cov: 32)
  • Exomes 𝑓: 0.63 (82845 hom.)
• Consequence: ME2 NM_002396.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.305

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ME2	NM_002396.5	c.*199G>A		3_prime_UTR_variant	16/16	ENST00000321341.11
ME2	NM_001168335.2	c.*344G>A		3_prime_UTR_variant	14/14
ME2	NR_174094.1	n.2086G>A		non_coding_transcript_exon_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ME2	ENST00000321341.11	c.*199G>A		3_prime_UTR_variant	16/16	1	NM_002396.5	P1

Frequencies

GnomAD3 genomes AF: 0.658 AC: 100004 AN: 151908 Hom.: 33185 Cov.: 32

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.673

GnomAD4 exome AF: 0.634 AC: 258469 AN: 407388 Hom.: 82845 Cov.: 4 AF XY: 0.641 AC XY: 136752 AN XY: 213372

Gnomad4 AFR exome AF: 0.737

Gnomad4 AMR exome AF: 0.743

Gnomad4 ASJ exome AF: 0.628

Gnomad4 EAS exome AF: 0.579

Gnomad4 SAS exome AF: 0.769

Gnomad4 FIN exome AF: 0.563

Gnomad4 NFE exome AF: 0.616

Gnomad4 OTH exome AF: 0.639

GnomAD4 genome AF: 0.658 AC: 100093 AN: 152026 Hom.: 33215 Cov.: 32 AF XY: 0.660 AC XY: 49000 AN XY: 74274

Gnomad4 AFR AF: 0.728

Gnomad4 AMR AF: 0.732

Gnomad4 ASJ AF: 0.647

Gnomad4 EAS AF: 0.593

Gnomad4 SAS AF: 0.766

Gnomad4 FIN AF: 0.554

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.669

Alfa AF: 0.633 Hom.: 30170

Bravo AF: 0.669

Asia WGS AF: 0.675 AC: 2347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.14
DANN	Benign	0.76

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: rs12277; hg19: chr18-48473753;