NM_002396.5:c.1418-1736T>C

Variant names:

• chr18-50937834-T-C
• rs654136
• NM_002396.5:c.1418-1736T>C

Variant summary

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

The NM_002396.5(ME2):​c.1418-1736T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 151,806 control chromosomes in the GnomAD database, including 19,013 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 0.49 (19013 hom., cov: 31)
• Consequence: ME2 NM_002396.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.113

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ME2	NM_002396.5	c.1418-1736T>C		intron_variant	Intron 13 of 15	ENST00000321341.11	NP_002387.1
ME2	NM_001168335.2	c.1417+5474T>C		intron_variant	Intron 13 of 13		NP_001161807.1
ME2	NR_174094.1	n.1621-2454T>C		intron_variant	Intron 13 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ME2	ENST00000321341.11	c.1418-1736T>C		intron_variant	Intron 13 of 15	1	NM_002396.5	ENSP00000321070.5

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74720 AN: 151688 Hom.: 19008 Cov.: 31

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.492 AC: 74749 AN: 151806 Hom.: 19013 Cov.: 31 AF XY: 0.495 AC XY: 36764 AN XY: 74200

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.619

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.489

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.509

Alfa AF: 0.530 Hom.: 44371

Bravo AF: 0.490

Asia WGS AF: 0.553 AC: 1924 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	2.4
DANN	Benign	0.73

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: rs654136; hg19: chr18-48464204;