rs6903252

Variant names:

• chr6-145601641-A-G
• rs6903252
• ENST00000638717.1:c.499+33604T>C

Variant summary

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

The ENST00000638717.1(EPM2A):​c.499+33604T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 152,034 control chromosomes in the GnomAD database, including 20,215 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 0.50 (20215 hom., cov: 32)
• Consequence: EPM2A ENST00000638717.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.726
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPM2A	XM_024446550.2	c.718+33604T>C		intron_variant	Intron 3 of 4		XP_024302318.1
EPM2A	XM_011536113.3	c.718+33604T>C		intron_variant	Intron 3 of 4		XP_011534415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPM2A	ENST00000638717.1	c.499+33604T>C		intron_variant	Intron 3 of 4	5		ENSP00000491330.1
EPM2A	ENST00000450221.6	c.340+33604T>C		intron_variant	Intron 2 of 3	3		ENSP00000414900.2

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76598 AN: 151916 Hom.: 20178 Cov.: 32

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.504 AC: 76687 AN: 152034 Hom.: 20215 Cov.: 32 AF XY: 0.506 AC XY: 37592 AN XY: 74314

African (AFR) AF: 0.647 AC: 26825 AN: 41444

American (AMR) AF: 0.386 AC: 5902 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1501 AN: 3470

East Asian (EAS) AF: 0.345 AC: 1786 AN: 5178

South Asian (SAS) AF: 0.565 AC: 2720 AN: 4816

European-Finnish (FIN) AF: 0.517 AC: 5466 AN: 10572

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 30969 AN: 67966

Other (OTH) AF: 0.492 AC: 1037 AN: 2106

Alfa AF: 0.470 Hom.: 8484

Bravo AF: 0.501

Asia WGS AF: 0.501 AC: 1743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.22
DANN	Benign	0.45
PhyloP100		-0.73

Splicing

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

Other links and lift over

dbSNP: rs6903252; hg19: chr6-145922777;