Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003988342 | SCV004804105 | uncertain significance | not specified | 2024-01-03 | criteria provided, single submitter | clinical testing | Variant summary: The variant involves the deletion of exons 15-22 in the A2ML1 gene. A presumed nomenclature of c.(1683+1_1684-1)_(2764+1_2765-1)del has been designated for the purposes of this classification. This Copy Number Variant (CNV) is expected to alter the reading frame and predicted to result in a truncation or absence of the encoded protein due to nonsense mediated decay (NMD). However, available evidence is not sufficient to establish whether loss-of-function variants in A2ML1 cause disease. The variant allele was found at a frequency of 4.9e-05 in 20338 control chromosomes (gnomAD, Structural Variants dataset). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.(1683+1_1684-1)_(2764+1_2765-1)del in individuals affected with Otitis Media, Susceptibility to and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |