Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001779472 | SCV002014905 | likely pathogenic | Bardet-Biedl syndrome | 2021-10-14 | criteria provided, single submitter | clinical testing | Variant summary: SDCCAG8 c.1356+1G>C 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: four predict the variant abolishes a 5 prme splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 250564 control chromosomes. To our knowledge, no occurrence of c.1356+1G>C in individuals affected with Bardet-Biedl Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
Labcorp Genetics |
RCV002541103 | SCV003345929 | likely pathogenic | Senior-Loken syndrome 7; Bardet-Biedl syndrome 16 | 2022-04-28 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 11 of the SDCCAG8 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 SDCCAG8 are known to be pathogenic (PMID: 20835237, 22190896). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SDCCAG8-related conditions. ClinVar contains an entry for this variant (Variation ID: 1321378). 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. |