rs748048885
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_005670.4(EPM2A):āc.631C>Gā(p.Pro211Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Consequence
EPM2A
NM_005670.4 missense
NM_005670.4 missense
Scores
6
12
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 4.17
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM1
In a domain Tyrosine-protein phosphatase (size 167) in uniprot entity EPM2A_HUMAN there are 10 pathogenic changes around while only 1 benign (91%) in NM_005670.4
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3544451).
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152106Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome 0.00000657 AC: 1AN: 152106Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74312
GnomAD4 genome
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1
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152106
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32
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1
AN XY:
74312
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ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
.;T;.;.;.;.;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;D;.;.;.;.;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;.;L;.;L;.;.;.
PrimateAI
Benign
T
PROVEAN
Benign
.;N;.;.;.;.;.;.;.
REVEL
Uncertain
Sift
Benign
.;T;.;.;.;.;.;.;.
Sift4G
Benign
.;T;.;T;T;.;.;.;.
Polyphen
0.080, 0.065
.;B;.;B;.;B;.;.;.
Vest4
0.31, 0.31, 0.36
MutPred
0.56
.;Loss of glycosylation at P211 (P = 0.0326);.;Loss of glycosylation at P211 (P = 0.0326);.;Loss of glycosylation at P211 (P = 0.0326);.;.;.;
MVP
0.98
MPC
0.24
ClinPred
D
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at