ClinVar Miner

Submissions for variant NM_004287.4(GOSR2):c.557_584del (p.Ala186fs) (rs796052541)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187620 SCV000241215 uncertain significance not provided 2018-08-15 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the GOSR2 gene. The c.557_584del28 variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The c.557_584del28 variant causes a frameshift starting with codon Alanine 186, changes this amino acid to a Valine residue, and creates a premature Stop codon at position 5 of the new reading frame, denoted p.Ala186ValfsX5. This variant is predicted to cause loss of normal protein function through protein truncation, as the last 27 amino acids are replaced with 4 incorrect amino acids. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000818051 SCV000958645 uncertain significance Progressive myoclonic epilepsy 2018-09-16 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the GOSR2 gene (p.Ala186Valfs*5). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 26 amino acids of the GOSR2 protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with GOSR2-related disease. ClinVar contains an entry for this variant (Variation ID: 205635). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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