rs11155431

Positions:

• chr6-145563882-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000450221.6(EPM2A):​c.341-61307T>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 ENST00000450221.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145

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 -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 41 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPM2A	XM_024446550.2	c.719-61307T>C		intron_variant			XP_024302318.1
EPM2A	XM_011536113.3	c.719-61307T>C		intron_variant			XP_011534415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPM2A	ENST00000638717.1	c.500-61307T>C		intron_variant		5		ENSP00000491330.1
EPM2A	ENST00000450221.6	c.341-61307T>C		intron_variant		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

Gnomad4 AFR AF: 0.00380

Gnomad4 AMR AF: 0.00942

Gnomad4 ASJ AF: 0.0317

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00456

Gnomad4 FIN AF: 0.0594

Gnomad4 NFE AF: 0.0285

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.0254 Hom.: 38

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11155431; hg19: chr6-145885018;