Genetic Variant ME2:c.*2896G>A (chr18-50950080-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002396.5(ME2):c.*2896G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,196 control chromosomes in the GnomAD database, including 3,918 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 0.20 ( 3918 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

ME2
NM_002396.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0330

Publications

4 publications found

Variant links:

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)

ME2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.285 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ME2	NM_002396.5	MANE Select	c.*2896G>A	3_prime_UTR	Exon 16 of 16	NP_002387.1
ME2	NR_174094.1		n.4783G>A	non_coding_transcript_exon	Exon 15 of 15
ME2	NM_001168335.2		c.*3041G>A	3_prime_UTR	Exon 14 of 14	NP_001161807.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ME2	ENST00000321341.11	TSL:1 MANE Select	c.*2896G>A		3_prime_UTR	Exon 16 of 16	ENSP00000321070.5

Frequencies

GnomAD3 genomes

AF:

0.204

AC:

31008

AN:

152078

Hom.:

3917

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0538

Gnomad AMI

AF:

0.456

Gnomad AMR

AF:

0.173

Gnomad ASJ

AF:

0.293

Gnomad EAS

AF:

0.298

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.327

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.270

Gnomad OTH

AF:

0.229

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.204

AC:

31006

AN:

152196

Hom.:

3918

Cov.:

AF XY:

0.205

AC XY:

15265

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0536

AC:

2227

AN:

41554

American (AMR)

AF:

0.173

AC:

2645

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.293

AC:

1018

AN:

3470

East Asian (EAS)

AF:

0.298

AC:

1543

AN:

5184

South Asian (SAS)

AF:

0.164

AC:

789

AN:

4820

European-Finnish (FIN)

AF:

0.327

AC:

3458

AN:

10566

Middle Eastern (MID)

AF:

0.255

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.270

AC:

18340

AN:

67992

Other (OTH)

AF:

0.235

AC:

496

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1230

2460

3691

4921

6151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

332

664

996

1328

1660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.250

Hom.:

9467

Bravo

AF:

0.191

Asia WGS

AF:

0.252

AC:

876

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.87

(source)

DANN

Benign

0.38

PhyloP100

0.033

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over