rs2328686

Variant names:

• chr6-145443150-T-C
• rs2328686
• ENST00000638717.1:c.554-59053A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000638717.1(EPM2A):​c.554-59053A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 152,122 control chromosomes in the GnomAD database, including 46,288 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.78 (46288 hom., cov: 32)
• Consequence: EPM2A ENST00000638717.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.12
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• Lafora disease

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000638717.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPM2A	ENST00000638717.1	TSL:5	c.554-59053A>G		intron	N/A	ENSP00000491330.1

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118295 AN: 152004 Hom.: 46271 Cov.: 32

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.902

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.786

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.778 AC: 118350 AN: 152122 Hom.: 46288 Cov.: 32 AF XY: 0.778 AC XY: 57831 AN XY: 74358

African (AFR) AF: 0.708 AC: 29354 AN: 41472

American (AMR) AF: 0.780 AC: 11923 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.821 AC: 2850 AN: 3472

East Asian (EAS) AF: 0.902 AC: 4668 AN: 5174

South Asian (SAS) AF: 0.741 AC: 3572 AN: 4822

European-Finnish (FIN) AF: 0.801 AC: 8482 AN: 10584

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.807 AC: 54884 AN: 67998

Other (OTH) AF: 0.779 AC: 1641 AN: 2106

Alfa AF: 0.794 Hom.: 6210

Bravo AF: 0.774

Asia WGS AF: 0.784 AC: 2727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.20
DANN	Benign	0.41
PhyloP100		-4.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2328686; hg19: chr6-145764286;