Variant 6-145735712-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001360064.2(EPM2A):c.-114+196A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 958,956 control chromosomes in the GnomAD database, including 232,615 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.73 ( 40512 hom., cov: 32)

Exomes 𝑓: 0.69 ( 192103 hom. )

Consequence

EPM2A
NM_001360064.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.711

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:

ENSG00000270638 (HGNC:):

ENSG00000270638 links:

EPM2A-DT (HGNC:48990): (EPM2A divergent transcript)

EPM2A-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 6-145735712-T-C is Benign according to our data. Variant chr6-145735712-T-C is described in ClinVar as [Benign]. Clinvar id is 670730.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
EPM2A	NM_001360064.2 link	c.-114+196A>G	intron_variant	Intron 1 of 3	NP_001346993.1
EPM2A-DT	NR_038246.1 link	n.52+792T>C	intron_variant	Intron 1 of 2
EPM2A	NR_153398.2 link	n.116+196A>G	intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
EPM2A	ENST00000639423.1 link	c.-114+196A>G	intron_variant	Intron 1 of 3	1	ENSP00000492701.1	O95278-8
EPM2A	ENST00000611340.5 link	c.-114+284A>G	intron_variant	Intron 1 of 3	2	ENSP00000480268.1	O95278-8
EPM2A	ENST00000640980.1 link	c.-114+196A>G	intron_variant	Intron 1 of 2	3	ENSP00000491191.1	A0A1W2PPJ6

Frequencies

GnomAD3 genomes

AF:

0.725

AC:

110173

AN:

151956

Hom.:

40470

Cov.:

show subpopulations

Gnomad AFR

AF:

0.815

Gnomad AMI

AF:

0.793

Gnomad AMR

AF:

0.802

Gnomad ASJ

AF:

0.690

Gnomad EAS

AF:

0.788

Gnomad SAS

AF:

0.599

Gnomad FIN

AF:

0.579

Gnomad MID

AF:

0.694

Gnomad NFE

AF:

0.681

Gnomad OTH

AF:

0.739

GnomAD4 exome

AF:

0.690

AC:

556707

AN:

806888

Hom.:

192103

Cov.:

AF XY:

0.689

AC XY:

261857

AN XY:

379790

show subpopulations

Gnomad4 AFR exome

AF:

0.820

Gnomad4 AMR exome

AF:

0.834

Gnomad4 ASJ exome

AF:

0.694

Gnomad4 EAS exome

AF:

0.788

Gnomad4 SAS exome

AF:

0.594

Gnomad4 FIN exome

AF:

0.637

Gnomad4 NFE exome

AF:

0.687

Gnomad4 OTH exome

AF:

0.702

GnomAD4 genome

AF:

0.725

AC:

110263

AN:

152068

Hom.:

40512

Cov.:

AF XY:

0.722

AC XY:

53652

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.815

Gnomad4 AMR

AF:

0.802

Gnomad4 ASJ

AF:

0.690

Gnomad4 EAS

AF:

0.788

Gnomad4 SAS

AF:

0.598

Gnomad4 FIN

AF:

0.579

Gnomad4 NFE

AF:

0.681

Gnomad4 OTH

AF:

0.733

Alfa

AF:

0.689

Hom.:

53743

Bravo

AF:

0.748

Asia WGS

AF:

0.678

AC:

2357

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

6.7

DANN

Benign

0.57

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