18-50918433-C-G

Variant names:

• chr18-50918433-C-G
• rs608986
• NM_002396.5:c.734+220C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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 (AFR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ME2	NM_002396.5	c.734+220C>G		intron_variant	Intron 7 of 15	ENST00000321341.11	NP_002387.1
ME2	NM_001168335.2	c.734+220C>G		intron_variant	Intron 7 of 13		NP_001161807.1
ME2	NR_174094.1	n.937+220C>G		intron_variant	Intron 7 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ME2	ENST00000321341.11	c.734+220C>G		intron_variant	Intron 7 of 15	1	NM_002396.5	ENSP00000321070.5

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

African (AFR) AF: 0.153 AC: 6368 AN: 41518

American (AMR) AF: 0.0347 AC: 530 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0528 AC: 183 AN: 3468

East Asian (EAS) AF: 0.0978 AC: 507 AN: 5186

South Asian (SAS) AF: 0.0728 AC: 351 AN: 4824

European-Finnish (FIN) AF: 0.0408 AC: 433 AN: 10610

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0305 AC: 2077 AN: 68034

Other (OTH) AF: 0.0649 AC: 137 AN: 2110

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
PhyloP100		0.048
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: rs608986; hg19: chr18-48444803;