rs1890199

Variant names:

• chr6-145384164-G-A
• rs1890199
• ENST00000638717.1:c.554-67C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000638717.1(EPM2A):​c.554-67C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 151,826 control chromosomes in the GnomAD database, including 10,933 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (10933 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: EPM2A ENST00000638717.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.13
• 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: ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 6-145384164-G-A is Benign according to our data. Variant chr6-145384164-G-A is described in ClinVar as Benign. ClinVar VariationId is 3255262.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.439 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

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.554-67C>T		intron	N/A	ENSP00000491330.1	A0A1W2PPT8

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56946 AN: 151710 Hom.: 10925 Cov.: 31

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.375 AC: 56998 AN: 151826 Hom.: 10933 Cov.: 31 AF XY: 0.379 AC XY: 28106 AN XY: 74184

African (AFR) AF: 0.287 AC: 11860 AN: 41396

American (AMR) AF: 0.372 AC: 5674 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1320 AN: 3468

East Asian (EAS) AF: 0.256 AC: 1323 AN: 5160

South Asian (SAS) AF: 0.455 AC: 2185 AN: 4802

European-Finnish (FIN) AF: 0.438 AC: 4605 AN: 10514

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28693 AN: 67936

Other (OTH) AF: 0.363 AC: 762 AN: 2098

Alfa AF: 0.378 Hom.: 1408

Bravo AF: 0.365

Asia WGS AF: 0.405 AC: 1408 AN: 3474

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.27
DANN	Benign	0.53
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs1890199; hg19: chr6-145705300;