NM_002396.5:c.*7287T>C

Variant names:

• chr18-50954471-T-C
• rs685373
• NM_002396.5:c.*7287T>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.*7287T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 151,898 control chromosomes in the GnomAD database, including 36,313 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 0.69 (36313 hom., cov: 30)
• Consequence: ME2 NM_002396.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.298
• Publications: 1 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002396.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ME2	NM_002396.5	MANE Select	c.*7287T>C		downstream_gene	N/A	NP_002387.1	P23368-1
	ME2	NM_001168335.2		c.*7432T>C		downstream_gene	N/A	NP_001161807.1	P23368-2
	ME2	NR_174094.1		n.*214T>C		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ME2	ENST00000321341.11	TSL:1 MANE Select	c.*7287T>C		downstream_gene	N/A	ENSP00000321070.5	P23368-1

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104380 AN: 151780 Hom.: 36281 Cov.: 30

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.787

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.703

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

GnomAD4 genome AF: 0.688 AC: 104468 AN: 151898 Hom.: 36313 Cov.: 30 AF XY: 0.688 AC XY: 51037 AN XY: 74218

African (AFR) AF: 0.775 AC: 32121 AN: 41420

American (AMR) AF: 0.762 AC: 11612 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2348 AN: 3472

East Asian (EAS) AF: 0.642 AC: 3309 AN: 5154

South Asian (SAS) AF: 0.787 AC: 3789 AN: 4812

European-Finnish (FIN) AF: 0.558 AC: 5881 AN: 10534

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.637 AC: 43312 AN: 67952

Other (OTH) AF: 0.699 AC: 1470 AN: 2104

Alfa AF: 0.667 Hom.: 7732

Bravo AF: 0.702

Asia WGS AF: 0.699 AC: 2432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.9
DANN	Benign	0.75
PhyloP100		-0.30

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs685373; hg19: chr18-48480841;