chr6-145384164-G-A

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPM2A	XM_024446550.2	c.773-67C>T		intron_variant	Intron 4 of 4		XP_024302318.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPM2A	ENST00000638717.1	c.554-67C>T		intron_variant	Intron 4 of 4	5		ENSP00000491330.1

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

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.363

Alfa AF: 0.382 Hom.: 1370

Bravo AF: 0.365

Asia WGS AF: 0.405 AC: 1408 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 59% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 55. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1890199; hg19: chr6-145705300;