Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV002064308 | SCV005359925 | uncertain significance | Glycogen storage disease, type II | 2024-08-06 | reviewed by expert panel | curation | The NM_000152.5:c c.1437+19G>A variant in GAA is an intronic variant located in intron 9 of the GAA gene. The computational splicing predictor SpliceAI gives a score of 0 for donor site loss, suggesting that the variant has no impact on splicing (BP4). The highest population minor allele frequency in gnomAD v4.1.0 is 0.002488 (15/6028 alleles) in the Middle Eastern population, which is higher than the ClinGen Lysosomal Diseases VCEP’s threshold for PM2 (<0.001), but lower than the threshold for BS1 (<0.005) and therefore does not meet either of these criteria. There is a ClinVar entry for this variant (Variation ID: 515407). In summary, this variant meets the criteria to be classified as uncertain significance for Pompe disease. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen Lysosomal Diseases Variant Curation Expert Panel (specifications Version 2.0): BP4. (Classification approved by the ClinGen Lysosomal Diseases Variant Curation Expert Panel on August 6, 2024). |
Gene |
RCV000608166 | SCV000727502 | likely benign | not specified | 2018-02-16 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Labcorp Genetics |
RCV002064308 | SCV002384305 | likely benign | Glycogen storage disease, type II | 2024-01-22 | criteria provided, single submitter | clinical testing |