Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002308564 | SCV002600443 | likely pathogenic | Spinocerebellar ataxia type 27 | 2022-10-11 | criteria provided, single submitter | clinical testing | Variant summary: FGF14 c.408+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 a canonical 5' splicing donor site, and two predict the variant abolishes a cryptic 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251390 control chromosomes (gnomAD). To our knowledge, no occurrence of c.408+1G>A in individuals affected with Spinocerebellar Ataxia Type 27 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. |
Prevention |
RCV003408225 | SCV004111330 | likely pathogenic | FGF14-related disorder | 2022-12-13 | criteria provided, single submitter | clinical testing | The FGF14 c.408+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Variants that disrupt the consensus splice donor site in FGF14 are expected to be pathogenic. This variant is interpreted as likely pathogenic. |