6-145627253-A-C

Position:

• chr6-145627253-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005670.4(EPM2A):​c.*163T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 1,529,212 control chromosomes in the GnomAD database, including 2,061 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.067 (1138 hom., cov: 33)
  • Exomes 𝑓: 0.0069 (923 hom.)
• Consequence: EPM2A NM_005670.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.970

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=-0.75).
• BP6: Variant 6-145627253-A-C is Benign according to our data. Variant chr6-145627253-A-C is described in ClinVar as [Benign]. Clinvar id is 1290853.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPM2A	NM_005670.4	c.*163T>G		3_prime_UTR_variant	4/4	ENST00000367519.9	NP_005661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPM2A	ENST00000367519.9	c.*163T>G		3_prime_UTR_variant	4/4	1	NM_005670.4	ENSP00000356489	P1

Frequencies

GnomAD3 genomes AF: 0.0666 AC: 10136 AN: 152162 Hom.: 1134 Cov.: 33

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0365

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00116

Gnomad OTH AF: 0.0616

GnomAD4 exome AF: 0.00685 AC: 9436 AN: 1376932 Hom.: 923 Cov.: 32 AF XY: 0.00597 AC XY: 4058 AN XY: 679224

Gnomad4 AFR exome AF: 0.236

Gnomad4 AMR exome AF: 0.0174

Gnomad4 ASJ exome AF: 0.00121

Gnomad4 EAS exome AF: 0.0000255

Gnomad4 SAS exome AF: 0.000465

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000570

Gnomad4 OTH exome AF: 0.0155

GnomAD4 genome AF: 0.0666 AC: 10146 AN: 152280 Hom.: 1138 Cov.: 33 AF XY: 0.0645 AC XY: 4805 AN XY: 74482

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.0365

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00116

Gnomad4 OTH AF: 0.0610

Alfa AF: 0.0103 Hom.: 216

Bravo AF: 0.0783

Asia WGS AF: 0.00837 AC: 30 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.8
DANN	Benign	0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7753694; hg19: chr6-145948389;