rs374338349
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1
The NM_005670.4(EPM2A):āc.136G>Cā(p.Ala46Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00384 in 788,066 control chromosomes in the GnomAD database, including 92 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A46T) has been classified as Uncertain significance.
Frequency
Consequence
NM_005670.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EPM2A | NM_005670.4 | c.136G>C | p.Ala46Pro | missense_variant | 1/4 | ENST00000367519.9 | |
EPM2A-DT | NR_038246.1 | n.52+443C>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EPM2A | ENST00000367519.9 | c.136G>C | p.Ala46Pro | missense_variant | 1/4 | 1 | NM_005670.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00431 AC: 602AN: 139548Hom.: 17 Cov.: 32
GnomAD3 exomes AF: 0.0103 AC: 117AN: 11398Hom.: 6 AF XY: 0.0108 AC XY: 79AN XY: 7306
GnomAD4 exome AF: 0.00373 AC: 2421AN: 648384Hom.: 75 Cov.: 24 AF XY: 0.00375 AC XY: 1196AN XY: 318756
GnomAD4 genome ? AF: 0.00436 AC: 609AN: 139682Hom.: 17 Cov.: 32 AF XY: 0.00523 AC XY: 354AN XY: 67748
ClinVar
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 16, 2015 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 08, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Lafora disease Benign:1Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 10, 2021 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 10, 2017 | This alteration is classified as 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. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 21, 2017 | - - |
Progressive myoclonic epilepsy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at