6-145735340-G-C

Position:

chr6-145735340-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005670.4(EPM2A):c.159C>G(p.Ala53Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 1,386,774 control chromosomes in the GnomAD database, including 246,746 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 30260 hom., cov: 31)

Exomes 𝑓: 0.59 ( 216486 hom. )

Consequence

EPM2A
NM_005670.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -0.643

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 6-145735340-G-C is Benign according to our data. Variant chr6-145735340-G-C is described in ClinVar as [Benign]. Clinvar id is 95306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-145735340-G-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.643 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPM2A	NM_005670.4 linkuse as main transcript	c.159C>G	p.Ala53Ala	synonymous_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.159C>G	p.Ala53Ala	synonymous_variant	1/4	1	NM_005670.4	ENSP00000356489.3		O95278-1

Frequencies

GnomAD3 genomes

AF:

0.631

AC:

94339

AN:

149600

Hom.:

30225

Cov.:

show subpopulations

Gnomad AFR

AF:

0.708

Gnomad AMI

AF:

0.634

Gnomad AMR

AF:

0.713

Gnomad ASJ

AF:

0.615

Gnomad EAS

AF:

0.742

Gnomad SAS

AF:

0.485

Gnomad FIN

AF:

0.504

Gnomad MID

AF:

0.554

Gnomad NFE

AF:

0.586

Gnomad OTH

AF:

0.643

GnomAD3 exomes

AF:

0.614

AC:

46781

AN:

76174

Hom.:

14895

AF XY:

0.591

AC XY:

25928

AN XY:

43850

show subpopulations

Gnomad AFR exome

AF:

0.687

Gnomad AMR exome

AF:

0.804

Gnomad ASJ exome

AF:

0.628

Gnomad EAS exome

AF:

0.764

Gnomad SAS exome

AF:

0.483

Gnomad FIN exome

AF:

0.528

Gnomad NFE exome

AF:

0.588

Gnomad OTH exome

AF:

0.622

GnomAD4 exome

AF:

0.589

AC:

728552

AN:

1237064

Hom.:

216486

Cov.:

AF XY:

0.585

AC XY:

355979

AN XY:

608792

show subpopulations

Gnomad4 AFR exome

AF:

0.706

Gnomad4 AMR exome

AF:

0.778

Gnomad4 ASJ exome

AF:

0.611

Gnomad4 EAS exome

AF:

0.727

Gnomad4 SAS exome

AF:

0.476

Gnomad4 FIN exome

AF:

0.522

Gnomad4 NFE exome

AF:

0.587

Gnomad4 OTH exome

AF:

0.598

GnomAD4 genome

AF:

0.631

AC:

94416

AN:

149710

Hom.:

30260

Cov.:

AF XY:

0.627

AC XY:

45811

AN XY:

73052

show subpopulations

Gnomad4 AFR

AF:

0.708

Gnomad4 AMR

AF:

0.714

Gnomad4 ASJ

AF:

0.615

Gnomad4 EAS

AF:

0.741

Gnomad4 SAS

AF:

0.486

Gnomad4 FIN

AF:

0.504

Gnomad4 NFE

AF:

0.586

Gnomad4 OTH

AF:

0.638

Alfa

AF:

0.507

Hom.:

1432

Bravo

AF:

0.653

Asia WGS

AF:

0.567

AC:

1844

AN:

3250

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 14, 2017	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 94% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 87. Only high quality variants are reported. -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 19, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 29, 2017	- -

Lafora disease

Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 08, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Progressive myoclonic epilepsy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

8.3

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over