Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003862245 | SCV004674436 | likely pathogenic | not provided | 2023-09-10 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with ANO10-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant is present in population databases (rs768148483, gnomAD 0.0009%). This sequence change affects a donor splice site in intron 6 of the ANO10 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 ANO10 are known to be pathogenic (PMID: 25089919). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004587575 | SCV005077389 | likely pathogenic | Autosomal recessive spinocerebellar ataxia 10 | 2024-04-05 | criteria provided, single submitter | clinical testing | Variant summary: ANO10 c.1162+1G>A 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 the canonical 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 250692 control chromosomes. To our knowledge, no occurrence of c.1162+1G>A in individuals affected with Spinocerebellar ataxia 10 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 3010606). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Fulgent Genetics, |
RCV004587575 | SCV005664515 | likely pathogenic | Autosomal recessive spinocerebellar ataxia 10 | 2024-01-31 | criteria provided, single submitter | clinical testing |