dbSNP rs1789223: ME2:c.1417+3480G>A (chr18-50935840-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.1417+3480G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 149,752 control chromosomes in the GnomAD database, including 34,993 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 0.68 ( 34987 hom., cov: 26)

Exomes 𝑓: 0.60 ( 6 hom. )

Consequence

ME2
NM_002396.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.220

Publications

6 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=-0.96).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ME2	NM_002396.5 link	c.1417+3480G>A	intron_variant	Intron 13 of 15	ENST00000321341.11	NP_002387.1	P23368-1
ME2	NM_001168335.2 link	c.1417+3480G>A	intron_variant	Intron 13 of 13		NP_001161807.1	P23368-2
ME2	NR_174094.1 link	n.1620+3480G>A	intron_variant	Intron 13 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ME2	ENST00000321341.11 link	c.1417+3480G>A		intron_variant	Intron 13 of 15	1	NM_002396.5	ENSP00000321070.5		P23368-1

Frequencies

GnomAD3 genomes

AF:

0.680

AC:

101708

AN:

149596

Hom.:

34951

Cov.:

show subpopulations

Gnomad AFR

AF:

0.777

Gnomad AMI

AF:

0.461

Gnomad AMR

AF:

0.749

Gnomad ASJ

AF:

0.650

Gnomad EAS

AF:

0.651

Gnomad SAS

AF:

0.783

Gnomad FIN

AF:

0.553

Gnomad MID

AF:

0.679

Gnomad NFE

AF:

0.624

Gnomad OTH

AF:

0.692

GnomAD4 exome

AF:

0.600

AC:

AN:

Hom.:

AF XY:

0.588

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

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)

AF:

0.531

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.680

AC:

101799

AN:

149712

Hom.:

34987

Cov.:

AF XY:

0.681

AC XY:

49674

AN XY:

72910

show subpopulations

African (AFR)

AF:

0.777

AC:

31514

AN:

40570

American (AMR)

AF:

0.749

AC:

11189

AN:

14938

Ashkenazi Jewish (ASJ)

AF:

0.650

AC:

2255

AN:

3470

East Asian (EAS)

AF:

0.651

AC:

3314

AN:

5090

South Asian (SAS)

AF:

0.783

AC:

3748

AN:

4788

European-Finnish (FIN)

AF:

0.553

AC:

5429

AN:

9824

Middle Eastern (MID)

AF:

0.683

AC:

198

AN:

290

European-Non Finnish (NFE)

AF:

0.624

AC:

42308

AN:

67762

Other (OTH)

AF:

0.687

AC:

1427

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1580

3160

4739

6319

7899

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

804

1608

2412

3216

4020

<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:

0.670

Hom.:

5007

Bravo

AF:

0.694

Asia WGS

AF:

0.701

AC:

2439

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

3.1

(source)

DANN

Benign

0.54

PhyloP100

-0.22

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over