Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV004586038 | SCV005075888 | pathogenic | Glucocorticoid deficiency with achalasia | 2024-04-02 | criteria provided, single submitter | clinical testing | Variant summary: AAAS c.446+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. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251432 control chromosomes (gnomAD). c.446+1G>A has been reported in the literature in individuals affected with Glucocorticoid Deficiency With Achalasia (Ismail_2006). These data indicate that the variant is likely to be associated with disease. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as pathogenic. |