Variant 6-145625944-C-T 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_005670.4(EPM2A):c.*1472G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 1,291,750 control chromosomes in the GnomAD database, including 123,836 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.46 ( 16539 hom., cov: 32)

Exomes 𝑓: 0.43 ( 107297 hom. )

Consequence

EPM2A
NM_005670.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.36

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:

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=-0.98).

BP6

Variant 6-145625944-C-T is Benign according to our data. Variant chr6-145625944-C-T is described in ClinVar as [Benign]. Clinvar id is 1230296.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.545 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.*1472G>A		3_prime_UTR_variant	4/4	ENST00000367519.9	NP_005661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPM2A	ENST00000367519.9 linkuse as main transcript	c.*1472G>A		3_prime_UTR_variant	4/4	1	NM_005670.4	ENSP00000356489	P1	O95278-1

Frequencies

GnomAD3 genomes

AF:

0.459

AC:

69701

AN:

151904

Hom.:

16513

Cov.:

show subpopulations

Gnomad AFR

AF:

0.551

Gnomad AMI

AF:

0.367

Gnomad AMR

AF:

0.346

Gnomad ASJ

AF:

0.392

Gnomad EAS

AF:

0.330

Gnomad SAS

AF:

0.534

Gnomad FIN

AF:

0.510

Gnomad MID

AF:

0.472

Gnomad NFE

AF:

0.430

Gnomad OTH

AF:

0.446

GnomAD4 exome

AF:

0.429

AC:

489474

AN:

1139728

Hom.:

107297

Cov.:

AF XY:

0.432

AC XY:

240347

AN XY:

556338

show subpopulations

Gnomad4 AFR exome

AF:

0.565

Gnomad4 AMR exome

AF:

0.296

Gnomad4 ASJ exome

AF:

0.397

Gnomad4 EAS exome

AF:

0.328

Gnomad4 SAS exome

AF:

0.536

Gnomad4 FIN exome

AF:

0.491

Gnomad4 NFE exome

AF:

0.424

Gnomad4 OTH exome

AF:

0.432

GnomAD4 genome

AF:

0.459

AC:

69772

AN:

152022

Hom.:

16539

Cov.:

AF XY:

0.461

AC XY:

34248

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.551

Gnomad4 AMR

AF:

0.345

Gnomad4 ASJ

AF:

0.392

Gnomad4 EAS

AF:

0.330

Gnomad4 SAS

AF:

0.534

Gnomad4 FIN

AF:

0.510

Gnomad4 NFE

AF:

0.430

Gnomad4 OTH

AF:

0.453

Alfa

AF:

0.431

Hom.:

3425

Bravo

AF:

0.450

Asia WGS

AF:

0.476

AC:

1655

AN:

3478

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.085

DANN

Benign

0.30

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