18-50920583-C-T

Variant names:

• chr18-50920583-C-T
• rs674210
• NM_002396.5:c.844+18C>T

Variant summary

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

The NM_002396.5(ME2):​c.844+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 1,563,810 control chromosomes in the GnomAD database, including 327,419 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 0.68 (35874 hom., cov: 31)
  • Exomes 𝑓: 0.64 (291545 hom.)
• Consequence: ME2 NM_002396.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.40

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ME2	NM_002396.5	c.844+18C>T		intron_variant	Intron 8 of 15	ENST00000321341.11	NP_002387.1
ME2	NM_001168335.2	c.844+18C>T		intron_variant	Intron 8 of 13		NP_001161807.1
ME2	NR_174094.1	n.1047+18C>T		intron_variant	Intron 8 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ME2	ENST00000321341.11	c.844+18C>T		intron_variant	Intron 8 of 15	1	NM_002396.5	ENSP00000321070.5

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103714 AN: 151856 Hom.: 35836 Cov.: 31

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.695

GnomAD3 exomes AF: 0.670 AC: 141952 AN: 211920 Hom.: 48276 AF XY: 0.669 AC XY: 77687 AN XY: 116042

Gnomad AFR exome AF: 0.792

Gnomad AMR exome AF: 0.780

Gnomad ASJ exome AF: 0.631

Gnomad EAS exome AF: 0.663

Gnomad SAS exome AF: 0.786

Gnomad FIN exome AF: 0.561

Gnomad NFE exome AF: 0.628

Gnomad OTH exome AF: 0.658

GnomAD4 exome AF: 0.640 AC: 903470 AN: 1411836 Hom.: 291545 Cov.: 25 AF XY: 0.644 AC XY: 452014 AN XY: 702298

Gnomad4 AFR exome AF: 0.803

Gnomad4 AMR exome AF: 0.774

Gnomad4 ASJ exome AF: 0.631

Gnomad4 EAS exome AF: 0.632

Gnomad4 SAS exome AF: 0.780

Gnomad4 FIN exome AF: 0.564

Gnomad4 NFE exome AF: 0.625

Gnomad4 OTH exome AF: 0.648

GnomAD4 genome AF: 0.683 AC: 103808 AN: 151974 Hom.: 35874 Cov.: 31 AF XY: 0.684 AC XY: 50818 AN XY: 74286

Gnomad4 AFR AF: 0.786

Gnomad4 AMR AF: 0.751

Gnomad4 ASJ AF: 0.650

Gnomad4 EAS AF: 0.658

Gnomad4 SAS AF: 0.783

Gnomad4 FIN AF: 0.558

Gnomad4 NFE AF: 0.624

Gnomad4 OTH AF: 0.691

Alfa AF: 0.646 Hom.: 6407

Bravo AF: 0.697

Asia WGS AF: 0.704 AC: 2450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.0050
DANN	Benign	0.32

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: rs674210; hg19: chr18-48446953;