ENST00000638717.1:c.553+16C>T

Variant names:

• chr6-145502508-G-A
• rs1779905194
• ENST00000638717.1:c.553+14C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000638717.1(EPM2A):​c.553+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000315 in 317,238 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: EPM2A ENST00000638717.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 0 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: ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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

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

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPM2A	ENST00000638717.1	TSL:5	c.553+14C>T		intron	N/A	ENSP00000491330.1	A0A1W2PPT8
	EPM2A	ENST00000450221.6	TSL:3	c.394+14C>T		intron	N/A	ENSP00000414900.2	H0Y7S8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000315 AC: 1 AN: 317238 Hom.: 0 Cov.: 0 AF XY: 0.00000558 AC XY: 1 AN XY: 179368

African (AFR) AF: 0.00 AC: 0 AN: 8578

American (AMR) AF: 0.00 AC: 0 AN: 27278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10788

East Asian (EAS) AF: 0.00 AC: 0 AN: 9194

South Asian (SAS) AF: 0.00 AC: 0 AN: 59660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26838

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1772

European-Non Finnish (NFE) AF: 0.00000629 AC: 1 AN: 158934

Other (OTH) AF: 0.00 AC: 0 AN: 14196

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.4
DANN	Benign	0.31
PhyloP100		0.36

Splicing

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

Other links and lift over

dbSNP: rs1779905194; hg19: chr6-145823644;