chr6-145735513-G-C

Variant names:

• chr6-145735513-G-C
• rs7771112
• NM_005670.4:c.-15C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005670.4(EPM2A):​c.-15C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000969 in 1,031,500 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 9.7e-7 (0 hom.)
• Consequence: EPM2A NM_005670.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.578
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005670.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPM2A	NM_005670.4	MANE Select	c.-15C>G		5_prime_UTR	Exon 1 of 4	NP_005661.1
	EPM2A	NM_001018041.2		c.-15C>G		5_prime_UTR	Exon 1 of 5	NP_001018051.1
	EPM2A	NM_001368130.1		c.-15C>G		5_prime_UTR	Exon 1 of 3	NP_001355059.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPM2A	ENST00000367519.9	TSL:1 MANE Select	c.-15C>G		5_prime_UTR	Exon 1 of 4	ENSP00000356489.3
	EPM2A	ENST00000639423.1	TSL:1	c.-114+395C>G		intron	N/A	ENSP00000492701.1
	EPM2A	ENST00000640297.1	TSL:5	n.2C>G		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.69e-7 AC: 1 AN: 1031500 Hom.: 0 Cov.: 35 AF XY: 0.00000205 AC XY: 1 AN XY: 487184

African (AFR) AF: 0.00 AC: 0 AN: 20804

American (AMR) AF: 0.00 AC: 0 AN: 6676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11896

East Asian (EAS) AF: 0.00 AC: 0 AN: 21678

South Asian (SAS) AF: 0.00 AC: 0 AN: 20016

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18950

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2616

European-Non Finnish (NFE) AF: 0.00000112 AC: 1 AN: 889102

Other (OTH) AF: 0.00 AC: 0 AN: 39762

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.9
DANN	Benign	0.87
PhyloP100		0.58
PromoterAI		-0.016	Neutral

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: rs7771112; hg19: chr6-146056649;