rs608781

Positions:

• chr18-50880956-C-T

Variant summary

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

The ENST00000321341.11(ME2):​c.-13+1648C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 152,236 control chromosomes in the GnomAD database, including 56,016 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 0.85 (56016 hom., cov: 33)
• Consequence: ME2 ENST00000321341.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ME2	NM_002396.5	c.-13+1648C>T		intron_variant		ENST00000321341.11	NP_002387.1
ME2	NM_001168335.2	c.-13+1648C>T		intron_variant			NP_001161807.1
ME2	NR_174094.1	n.191+1648C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ME2	ENST00000321341.11	c.-13+1648C>T		intron_variant		1	NM_002396.5	ENSP00000321070	P1

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129421 AN: 152118 Hom.: 56002 Cov.: 33

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.935

Gnomad AMR AF: 0.893

Gnomad ASJ AF: 0.854

Gnomad EAS AF: 0.901

Gnomad SAS AF: 0.905

Gnomad FIN AF: 0.941

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.926

Gnomad OTH AF: 0.852

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

GnomAD4 genome AF: 0.851 AC: 129484 AN: 152236 Hom.: 56016 Cov.: 33 AF XY: 0.852 AC XY: 63398 AN XY: 74444

Gnomad4 AFR AF: 0.673

Gnomad4 AMR AF: 0.894

Gnomad4 ASJ AF: 0.854

Gnomad4 EAS AF: 0.901

Gnomad4 SAS AF: 0.905

Gnomad4 FIN AF: 0.941

Gnomad4 NFE AF: 0.926

Gnomad4 OTH AF: 0.853

Alfa AF: 0.884 Hom.: 7471

Bravo AF: 0.840

Asia WGS AF: 0.899 AC: 3125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.21
DANN	Benign	0.17

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: rs608781; hg19: chr18-48407326;