Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001203086 | SCV001374232 | uncertain significance | Progressive myoclonic epilepsy | 2022-08-09 | criteria provided, single submitter | clinical testing | This sequence change affects codon 112 of the GOSR2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the GOSR2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs755211944, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with GOSR2-related conditions. ClinVar contains an entry for this variant (Variation ID: 934652). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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. |
| Center for Genomics, |
RCV002071860 | SCV002495788 | uncertain significance | Progressive myoclonic epilepsy type 6 | 2021-06-16 | criteria provided, single submitter | clinical testing | GOSR2 NM_004287.4 exon 4 p.Asn112= (c.336C>T): This variant has not been reported in the literature and is not present in large control databases. This variant is present in ClinVar (Variation ID:034652). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. Of note, this variant is a silent variant and does not change the amino acid, reducing the probability that this variant is disease causing. However, this variant occurs in the last nucleotide of the exon; variants in this position may affect splicing. Splice prediction tools do not suggest that this variant may affect splicing. However, further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |
| Ambry Genetics | RCV002451421 | SCV002615520 | likely benign | Inborn genetic diseases | 2018-03-29 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: 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. |