rs11155431

Variant names:

• chr6-145563882-A-G
• rs11155431
• ENST00000638717.1:c.500-61307T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000638717.1(EPM2A):​c.500-61307T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0201 in 152,298 control chromosomes in the GnomAD database, including 41 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 0.020 (41 hom., cov: 32)
• Consequence: EPM2A ENST00000638717.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145
• Publications: 1 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=-0.95).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0201 (3054/152298) while in subpopulation NFE AF = 0.0285 (1939/68024). AF 95% confidence interval is 0.0274. There are 41 homozygotes in GnomAd4. There are 1511 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 41 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPM2A	XM_024446550.2	c.719-61307T>C		intron_variant	Intron 3 of 4		XP_024302318.1
EPM2A	XM_011536113.3	c.719-61307T>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.500-61307T>C		intron_variant	Intron 3 of 4	5		ENSP00000491330.1
EPM2A	ENST00000450221.6	c.341-61307T>C		intron_variant	Intron 2 of 3	3		ENSP00000414900.2

Frequencies

GnomAD3 genomes AF: 0.0201 AC: 3052 AN: 152180 Hom.: 41 Cov.: 32

Gnomad AFR AF: 0.00381

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.00943

Gnomad ASJ AF: 0.0317

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00456

Gnomad FIN AF: 0.0594

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0285

Gnomad OTH AF: 0.0153

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

GnomAD4 genome AF: 0.0201 AC: 3054 AN: 152298 Hom.: 41 Cov.: 32 AF XY: 0.0203 AC XY: 1511 AN XY: 74478

African (AFR) AF: 0.00380 AC: 158 AN: 41574

American (AMR) AF: 0.00942 AC: 144 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0317 AC: 110 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.00456 AC: 22 AN: 4824

European-Finnish (FIN) AF: 0.0594 AC: 631 AN: 10616

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0285 AC: 1939 AN: 68024

Other (OTH) AF: 0.0156 AC: 33 AN: 2112

Alfa AF: 0.0254 Hom.: 116

Bravo AF: 0.0158

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.4
DANN	Benign	0.60
PhyloP100		0.14

Splicing

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

Other links and lift over

dbSNP: rs11155431; hg19: chr6-145885018;