rs645088

chr18-50930533-T-Cchr18-50930533-T-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• 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/exons	MANE	UniProt
ME2	NM_002396.5	c.1315-1725T>C		intron_variant		ENST00000321341.11
ME2	NM_001168335.2	c.1315-1725T>C		intron_variant
ME2	NR_174094.1	n.1518-1725T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ME2	ENST00000321341.11	c.1315-1725T>C		intron_variant		1	NM_002396.5	P1

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

Gnomad4 AFR AF: 0.786

Gnomad4 AMR AF: 0.752

Gnomad4 ASJ AF: 0.650

Gnomad4 EAS AF: 0.651

Gnomad4 SAS AF: 0.783

Gnomad4 FIN AF: 0.559

Gnomad4 NFE AF: 0.624

Gnomad4 OTH AF: 0.692

Alfa AF: 0.642 Hom.: 29939

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

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: rs645088; hg19: chr18-48456903;