Variant 6-145501856-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000450221.6(EPM2A):c.395-9T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 470,816 control chromosomes in the GnomAD database, including 52,840 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.45 ( 15454 hom., cov: 32)

Exomes 𝑓: 0.48 ( 37386 hom. )

Consequence

EPM2A
ENST00000450221.6 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.307

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 6-145501856-A-G is Benign according to our data. Variant chr6-145501856-A-G is described in ClinVar as [Benign]. Clinvar id is 3255258.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-145501856-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPM2A	XM_011536113.3 linkuse as main transcript	c.772+666T>C		intron_variant			XP_011534415.1
EPM2A	XM_024446550.2 linkuse as main transcript	c.772+666T>C		intron_variant			XP_024302318.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPM2A	ENST00000450221.6 linkuse as main transcript	c.395-9T>C		splice_polypyrimidine_tract_variant, intron_variant		3		ENSP00000414900
EPM2A	ENST00000638717.1 linkuse as main transcript	c.555+666T>C		intron_variant		5		ENSP00000491330

Frequencies

GnomAD3 genomes

AF:

0.450

AC:

68398

AN:

151940

Hom.:

15431

Cov.:

show subpopulations

Gnomad AFR

AF:

0.413

Gnomad AMI

AF:

0.438

Gnomad AMR

AF:

0.413

Gnomad ASJ

AF:

0.455

Gnomad EAS

AF:

0.428

Gnomad SAS

AF:

0.584

Gnomad FIN

AF:

0.517

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.463

Gnomad OTH

AF:

0.440

GnomAD3 exomes

AF:

0.470

AC:

70051

AN:

148992

Hom.:

16848

AF XY:

0.480

AC XY:

38502

AN XY:

80256

show subpopulations

Gnomad AFR exome

AF:

0.417

Gnomad AMR exome

AF:

0.401

Gnomad ASJ exome

AF:

0.450

Gnomad EAS exome

AF:

0.413

Gnomad SAS exome

AF:

0.584

Gnomad FIN exome

AF:

0.512

Gnomad NFE exome

AF:

0.463

Gnomad OTH exome

AF:

0.463

GnomAD4 exome

AF:

0.479

AC:

152807

AN:

318758

Hom.:

37386

Cov.:

AF XY:

0.490

AC XY:

88182

AN XY:

180078

show subpopulations

Gnomad4 AFR exome

AF:

0.421

Gnomad4 AMR exome

AF:

0.402

Gnomad4 ASJ exome

AF:

0.451

Gnomad4 EAS exome

AF:

0.417

Gnomad4 SAS exome

AF:

0.577

Gnomad4 FIN exome

AF:

0.512

Gnomad4 NFE exome

AF:

0.460

Gnomad4 OTH exome

AF:

0.472

GnomAD4 genome

AF:

0.450

AC:

68465

AN:

152058

Hom.:

15454

Cov.:

AF XY:

0.456

AC XY:

33870

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.413

Gnomad4 AMR

AF:

0.413

Gnomad4 ASJ

AF:

0.455

Gnomad4 EAS

AF:

0.428

Gnomad4 SAS

AF:

0.584

Gnomad4 FIN

AF:

0.517

Gnomad4 NFE

AF:

0.463

Gnomad4 OTH

AF:

0.446

Alfa

AF:

0.441

Hom.:

4923

Bravo

AF:

0.438

Asia WGS

AF:

0.532

AC:

1850

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

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 62% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 58. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

1.5

DANN

Benign

0.42

Splicing

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