6-145669661-T-C

Position:

• chr6-145669661-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005670.4(EPM2A):​c.476+16461A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 152,024 control chromosomes in the GnomAD database, including 29,848 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 0.62 (29848 hom., cov: 32)
• Consequence: EPM2A NM_005670.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPM2A	NM_005670.4	c.476+16461A>G		intron_variant		ENST00000367519.9	NP_005661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPM2A	ENST00000367519.9	c.476+16461A>G		intron_variant		1	NM_005670.4	ENSP00000356489.3

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94582 AN: 151906 Hom.: 29816 Cov.: 32

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.709

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.636

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

GnomAD4 genome AF: 0.623 AC: 94654 AN: 152024 Hom.: 29848 Cov.: 32 AF XY: 0.619 AC XY: 45994 AN XY: 74308

Gnomad4 AFR AF: 0.683

Gnomad4 AMR AF: 0.710

Gnomad4 ASJ AF: 0.615

Gnomad4 EAS AF: 0.741

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.508

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.631

Alfa AF: 0.632 Hom.: 5174

Bravo AF: 0.644

Asia WGS AF: 0.587 AC: 2043 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.58
DANN	Benign	0.59

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: rs702304; hg19: chr6-145990797; COSMIC: COSV62297958; COSMIC: COSV62297958;