Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000792622 | SCV000931928 | likely pathogenic | not provided | 2023-10-05 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 11 of the EYS gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in EYS are known to be pathogenic (PMID: 18836446, 20333770). This variant is present in population databases (rs776204925, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with EYS-related conditions. ClinVar contains an entry for this variant (Variation ID: 639739). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001260372 | SCV001437329 | likely pathogenic | Retinitis pigmentosa | 2020-09-28 | criteria provided, single submitter | clinical testing | Variant summary: EYS c.1766+1G>T is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Three predict the variant abolishes a 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 2.4e-05 in 249334 control chromosomes. To our knowledge, no occurrence of c.1766+1G>T in individuals affected with Retinitis Pigmentosa and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, citing the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
Gene |
RCV000792622 | SCV003842438 | likely pathogenic | not provided | 2023-03-10 | criteria provided, single submitter | clinical testing | Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Reported as likely pathogenic in published literature, but additional evidence is not available (Hanany et al., 2020); This variant is associated with the following publications: (PMID: 31964843) |
Baylor Genetics | RCV001830688 | SCV004195215 | likely pathogenic | Retinitis pigmentosa 25 | 2023-08-12 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001830688 | SCV002076656 | likely pathogenic | Retinitis pigmentosa 25 | 2020-08-25 | no assertion criteria provided | clinical testing |