Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000423940 | SCV000517245 | pathogenic | not provided | 2022-08-30 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on splicing; This variant is associated with the following publications: (PMID: 17159980, 17503513, 33397523) |
Eurofins Ntd Llc |
RCV000423940 | SCV000706697 | pathogenic | not provided | 2017-03-06 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000763141 | SCV000893701 | pathogenic | Autosomal recessive ataxia, Beauce type; Emery-Dreifuss muscular dystrophy 4, autosomal dominant | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000423940 | SCV002018913 | pathogenic | not provided | 2023-06-27 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003330382 | SCV004038451 | pathogenic | Emery-Dreifuss muscular dystrophy 4, autosomal dominant | 2023-08-08 | criteria provided, single submitter | clinical testing | Variant summary: SYNE1 c.15705-12A>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Three predict the variant abolishes or weakens the canonical 3' acceptor site and four predict the variant creates a new 3' acceptor site. At least one publication reports experimental evidence that this variant indeed affects mRNA splicing through the use of a newly created 3' acceptor site which results in the inclusion of intronic material, creating a premature termination codon (Gros-Louis_2007). The variant allele was found at a frequency of 3.2e-05 in 251248 control chromosomes (gnomAD). c.15705-12A>G has been reported in the literature as a biallelic genotype in many French-Canadian individuals from multiple families affected with autosomal recessive cerebellar ataxia type 1 (ARCA1) (e.g. Gros-Louis_2007, Haj Salem_2021). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 17159980, 33397523). Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
OMIM | RCV000002416 | SCV000022574 | pathogenic | Autosomal recessive ataxia, Beauce type | 2007-07-01 | no assertion criteria provided | literature only |