ClinVar Miner

Submissions for variant NM_130837.3(OPA1):c.2287del (p.Ser763fs)

dbSNP: rs1219753329
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital RCV001249637 SCV001423604 pathogenic Abortive cerebellar ataxia; Optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy; Autosomal dominant optic atrophy classic form 2017-09-20 criteria provided, single submitter clinical testing [ACMG/AMP: PVS1, PM2] This alteration is a null variant in a gene where LOF is a known mechanism of disease [PVS1], is absent from or rarely observed in large-scale population databases [PM2].
GeneDx RCV001587285 SCV001822388 pathogenic not provided 2023-12-15 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32371413, 35741767, 21036400)
Labcorp Genetics (formerly Invitae), Labcorp RCV001587285 SCV002239002 pathogenic not provided 2023-10-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser708Valfs*15) in the OPA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in OPA1 are known to be pathogenic (PMID: 11440988, 20157015, 20952381, 25012220). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with autosomal dominant optic atrophy (PMID: 21036400). ClinVar contains an entry for this variant (Variation ID: 973235). For these reasons, this variant has been classified as Pathogenic.
Athena Diagnostics RCV001587285 SCV002771115 pathogenic not provided 2022-01-21 criteria provided, single submitter clinical testing This variant is expected to result in the loss of a functional protein. The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with this gene. In some published literature, this variant is referred to as c.2287delA, p.(Ser763ValfsTer15).
PreventionGenetics, part of Exact Sciences RCV004538529 SCV004119705 pathogenic OPA1-related disorder 2023-09-25 criteria provided, single submitter clinical testing The OPA1 c.2287delA variant is predicted to result in a frameshift and premature protein termination (p.Ser763Valfs*15). This variant has been reported in the heterozygous state in an individual with optic neuropathy (reported as c.2122del in Yu-Wai-Man et al. 2011. PubMed ID: 21036400). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-193374974-GA-G). Frameshift variants in OPA1 are expected to be pathogenic, and this variant has been interpreted as pathogenic by multiple independent submitters to the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/973235). Given the evidence, we too interpret c.2287del (p.Ser763Valfs*15) as pathogenic.

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