rs547147183

Variant names:

• chr6-145735370-G-A
• rs547147183
• NM_005670.4:c.129C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-145735370-G-A
• chr6-145735370-G-C
• chr6-145735370-G-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_005670.4(EPM2A):​c.129C>T​(p.Ala43Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,101,324 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. Synonymous variant affecting the same amino acid position (i.e. A43A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: EPM2A NM_005670.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• 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]

ENSG00000288551 (HGNC:):

EPM2A-DT (HGNC:48990): (EPM2A divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=-0.001 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPM2A	NM_005670.4	c.129C>T	p.Ala43Ala	synonymous_variant	Exon 1 of 4	ENST00000367519.9	NP_005661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPM2A	ENST00000367519.9	c.129C>T	p.Ala43Ala	synonymous_variant	Exon 1 of 4	1	NM_005670.4	ENSP00000356489.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1101324 Hom.: 0 Cov.: 36 AF XY: 0.00000375 AC XY: 2 AN XY: 533180

African (AFR) AF: 0.00 AC: 0 AN: 21534

American (AMR) AF: 0.00 AC: 0 AN: 8740

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13214

East Asian (EAS) AF: 0.00 AC: 0 AN: 22096

South Asian (SAS) AF: 0.00 AC: 0 AN: 33788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2880

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 934154

Other (OTH) AF: 0.0000468 AC: 2 AN: 42718

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	5.9
DANN	Benign	0.83
PhyloP100		-0.0010
PromoterAI		-0.081	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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

Other links and lift over

dbSNP: rs547147183; hg19: chr6-146056506;