ClinVar Miner

Submissions for variant NM_001135651.3(EIF2AK2):c.388G>A (p.Gly130Arg)

dbSNP: rs2148705154
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
SIB Swiss Institute of Bioinformatics RCV001807542 SCV002526424 likely pathogenic Dystonia 33 2022-06-10 criteria provided, single submitter curation This variant is interpreted as likely pathogenic for Dystonia 33, autosomal dominant. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PP1 upgraded to moderate); Prevalence in affected individuals statistically increased over controls (PS4 downgraded to supporting); Assumed de novo, but no confirmation of paternity and maternity (PM6); Well-established functional studies show a deleterious effect (PS3 downgraded to supporting).
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München RCV001807542 SCV002764683 pathogenic Dystonia 33 2020-12-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003660903 SCV004376242 pathogenic not provided 2022-11-06 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 130 of the EIF2AK2 protein (p.Gly130Arg). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with EIF2AK2-related conditions (PMID: 33236446, 33866603). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1332908). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV001807542 SCV002054134 pathogenic Dystonia 33 2022-02-10 no assertion criteria provided literature only

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