6-145625944-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.36

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]

ACMG classification

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	UniProt
EPM2A	NM_005670.4	c.*1472G>A		3_prime_UTR_variant	4/4	ENST00000367519.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPM2A	ENST00000367519.9	c.*1472G>A		3_prime_UTR_variant	4/4	1	NM_005670.4	P1

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69701 AN: 151904 Hom.: 16513 Cov.: 32

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.: 14 AF XY: 0.432 AC XY: 240347 AN XY: 556338

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.: 32 AF XY: 0.461 AC XY: 34248 AN XY: 74306

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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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

Other links and lift over

dbSNP: rs1045820; hg19: chr6-145947080; COSMIC: COSV62295394; COSMIC: COSV62295394;