Variant 6-145735351-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005670.4(EPM2A):c.148G>C(p.Gly50Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000831 in 1,204,006 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000085 ( 1 hom. )

Consequence

EPM2A
NM_005670.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.706

Variant links:

Genes affected

EPM2A (HGNC:3413): (EPM2A glucan phosphatase, laforin) This gene encodes a dual-specificity phosphatase and may be involved in the regulation of glycogen metabolism. The protein acts on complex carbohydrates to prevent glycogen hyperphosphorylation, thus avoiding the formation of insoluble aggregates. Loss-of-function mutations in this gene have been associated with Lafora disease, a rare, adult-onset recessive neurodegenerative disease, which results in myoclonus epilepsy and usually results in death several years after the onset of symptoms. The disease is characterized by the accumulation of insoluble particles called Lafora bodies, which are derived from glycogen. [provided by RefSeq, Jan 2018]

EPM2A links:

EPM2A (HGNC:):

EPM2A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31423646).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPM2A	NM_005670.4 linkuse as main transcript	c.148G>C	p.Gly50Arg	missense_variant	1/4	ENST00000367519.9	NP_005661.1	O95278-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPM2A	ENST00000367519.9 linkuse as main transcript	c.148G>C	p.Gly50Arg	missense_variant	1/4	1	NM_005670.4	ENSP00000356489.3		O95278-1

Frequencies

GnomAD3 genomes

AF:

0.00000684

AC:

AN:

146190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000151

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000238

AC:

AN:

41974

Hom.:

AF XY:

0.0000392

AC XY:

AN XY:

25512

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000578

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000851

AC:

AN:

1057816

Hom.:

Cov.:

AF XY:

0.00000969

AC XY:

AN XY:

516144

show subpopulations

Gnomad4 AFR exome

AF:

0.0000992

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000419

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000448

Gnomad4 OTH exome

AF:

0.0000260

GnomAD4 genome

AF:

0.00000684

AC:

AN:

146190

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

71204

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000151

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.38

T;.;.;.

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.68

T;T;.;T

M_CAP

Pathogenic

0.90

MetaRNN

Benign

0.31

T;T;T;T

MetaSVM

Uncertain

0.19

MutationAssessor

Benign

0.90

L;L;L;L

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.72

N;.;.;.

REVEL

Uncertain

0.30

Sift

Uncertain

0.024

D;.;.;.

Sift4G

Uncertain

0.032

D;D;.;.

Polyphen

0.0050

B;P;P;.

Vest4

0.15

MutPred

0.34

Gain of methylation at G50 (P = 0.0175);Gain of methylation at G50 (P = 0.0175);Gain of methylation at G50 (P = 0.0175);Gain of methylation at G50 (P = 0.0175);

MVP

0.92

MPC

0.33

ClinPred

0.20

GERP RS

2.5

gMVP

0.44

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over