Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001056224 | SCV001220656 | pathogenic | Retinitis pigmentosa 12; Leber congenital amaurosis 8 | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 11 of the CRB1 gene. It does not directly change the encoded amino acid sequence of the CRB1 protein. This variant is present in population databases (rs766850702, gnomAD 0.002%). This variant has been observed in individual(s) with clinical features of CRB1-related conditions (PMID: 24512366; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as IVS11-10A>G. ClinVar contains an entry for this variant (Variation ID: 851764). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Blueprint Genetics | RCV001074118 | SCV001239687 | likely pathogenic | Retinal dystrophy | 2019-01-15 | criteria provided, single submitter | clinical testing | |
| Centre for Mendelian Genomics, |
RCV001197156 | SCV001367792 | uncertain significance | Pigmented paravenous retinochoroidal atrophy | 2019-02-24 | criteria provided, single submitter | clinical testing | This variant was classified as: Uncertain significance. The available evidence favors the pathogenic nature of this variant, however the currently available data is insufficient to conclusively support its pathogenic nature. Thus this variant is classified as Uncertain significance - favor pathogenic. The following ACMG criteria were applied in classifying this variant: PM2. |
| Ocular Genomics Institute, |
RCV001376226 | SCV001573297 | uncertain significance | Retinitis pigmentosa 12 | 2021-04-08 | criteria provided, single submitter | research | The CRB1 c.4006-10A>G variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PM2. Based on this evidence we have classified this variant as Variant of Uncertain Significance. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001074118 | SCV004037971 | likely pathogenic | Retinal dystrophy | 2023-08-17 | criteria provided, single submitter | clinical testing | Variant summary: CRB1 c.4006-10A>G alters a conserved nucleotide located at a position not widely known to affect splicing. Several computational tools predict a significant impact on normal splicing: One predicts the variant abolishes a 3 acceptor site. Two predict the variant weakens a 3 acceptor site. Two predict the variant creates a cryptic 3 acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8e-06 in 251020 control chromosomes (gnomAD and publication data). c.4006-10A>G has been reported in the literature in individuals affected with Retinal Dystrophy (Cordovez_2015, Colombo_2021, Daich Varela_2022, Karali_2022). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 33576794, 24512366, 36099972, 34758253). Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified this variant as uncertain significance (n=2), likely pathogenic (n=1) and pathogenic (n=1). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV003473660 | SCV004211107 | pathogenic | Leber congenital amaurosis 8 | 2023-10-24 | criteria provided, single submitter | clinical testing | |
| Genomics England Pilot Project, |
RCV001376226 | SCV001760001 | likely pathogenic | Retinitis pigmentosa 12 | no assertion criteria provided | clinical testing |