NM_002396.5:c.1315-1725T>C

Variant names:

• chr18-50930533-T-C
• rs645088
• NM_002396.5:c.1315-1725T>C

Variant summary

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

The NM_002396.5(ME2):​c.1315-1725T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 152,054 control chromosomes in the GnomAD database, including 35,902 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency: Genomes: 𝑓 0.68 (35902 hom., cov: 31)
• Consequence: ME2 NM_002396.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.506
• Publications: 9 publications found

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]

ME2 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• 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.1315-1725T>C		intron_variant	Intron 12 of 15	ENST00000321341.11	NP_002387.1
ME2	NM_001168335.2	c.1315-1725T>C		intron_variant	Intron 12 of 13		NP_001161807.1
ME2	NR_174094.1	n.1518-1725T>C		intron_variant	Intron 12 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ME2	ENST00000321341.11	c.1315-1725T>C		intron_variant	Intron 12 of 15	1	NM_002396.5	ENSP00000321070.5

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103771 AN: 151934 Hom.: 35864 Cov.: 31

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.682

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.696

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

GnomAD4 genome AF: 0.683 AC: 103865 AN: 152054 Hom.: 35902 Cov.: 31 AF XY: 0.684 AC XY: 50839 AN XY: 74298

African (AFR) AF: 0.786 AC: 32594 AN: 41482

American (AMR) AF: 0.752 AC: 11470 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 2253 AN: 3468

East Asian (EAS) AF: 0.651 AC: 3365 AN: 5166

South Asian (SAS) AF: 0.783 AC: 3776 AN: 4822

European-Finnish (FIN) AF: 0.559 AC: 5897 AN: 10558

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.624 AC: 42436 AN: 67986

Other (OTH) AF: 0.692 AC: 1456 AN: 2104

Alfa AF: 0.649 Hom.: 40404

Bravo AF: 0.697

Asia WGS AF: 0.702 AC: 2442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.5
DANN	Benign	0.56
PhyloP100		0.51
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: rs645088; hg19: chr18-48456903;