rs587780938
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BS1BS2
The NM_005670.4(EPM2A):c.24G>A(p.Val8Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,212,804 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_005670.4 synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000772 AC: 117AN: 151476Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000551 AC: 3AN: 5446Hom.: 0 AF XY: 0.000614 AC XY: 2AN XY: 3258
GnomAD4 exome AF: 0.00159 AC: 1691AN: 1061220Hom.: 4 Cov.: 34 AF XY: 0.00155 AC XY: 787AN XY: 506852
GnomAD4 genome AF: 0.000772 AC: 117AN: 151584Hom.: 0 Cov.: 33 AF XY: 0.000635 AC XY: 47AN XY: 74074
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
- -
- -
EPM2A: BP4, BP7 -
not specified Benign:2
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
- -
Lafora disease Benign:1
This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF 0.1% (95/67772) (https://gnomad.broadinstitute.org/variant/6-145735475-C-T?dataset=gnomad_r3). This variant is present in ClinVar, with multiple classifications of Likely Benign or Benign (Variation ID:137222). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. Of note, this variant is a silent variant and does not change the amino acid, reducing the probability that this variant is disease causing. In summary, data on this variant suggests that this variant does not cause disease but requires further evidence. Therefore, this variant is classified as likely benign. -
Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Progressive myoclonic epilepsy Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at