rs608986

Positions:

• chr18-50918433-C-G
• chr18-50918433-C-T

Variant summary

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

The NM_002396.5(ME2):​c.734+220C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0698 in 152,240 control chromosomes in the GnomAD database, including 560 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 0.070 (560 hom., cov: 32)
• Consequence: ME2 NM_002396.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ME2	NM_002396.5	c.734+220C>G		intron_variant		ENST00000321341.11	NP_002387.1
ME2	NM_001168335.2	c.734+220C>G		intron_variant			NP_001161807.1
ME2	NR_174094.1	n.937+220C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ME2	ENST00000321341.11	c.734+220C>G		intron_variant		1	NM_002396.5	ENSP00000321070	P1

Frequencies

GnomAD3 genomes AF: 0.0697 AC: 10600 AN: 152122 Hom.: 560 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0348

Gnomad ASJ AF: 0.0528

Gnomad EAS AF: 0.0975

Gnomad SAS AF: 0.0727

Gnomad FIN AF: 0.0408

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0305

Gnomad OTH AF: 0.0651

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

GnomAD4 genome AF: 0.0698 AC: 10619 AN: 152240 Hom.: 560 Cov.: 32 AF XY: 0.0710 AC XY: 5286 AN XY: 74454

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.0347

Gnomad4 ASJ AF: 0.0528

Gnomad4 EAS AF: 0.0978

Gnomad4 SAS AF: 0.0728

Gnomad4 FIN AF: 0.0408

Gnomad4 NFE AF: 0.0305

Gnomad4 OTH AF: 0.0649

Alfa AF: 0.0231 Hom.: 20

Bravo AF: 0.0719

Asia WGS AF: 0.0750 AC: 264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.9
DANN	Benign	0.61

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: rs608986; hg19: chr18-48444803;