Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000813887 | SCV000954269 | pathogenic | Glycogen storage disease, type II | 2018-12-03 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exon 18 of the GAA gene. This leads to an in-frame deletion, preserving the integrity of the reading frame. Loss-of-function variants, including gross deletions, in GAA are known to be pathogenic. Deletion of exon 18 has been reported in the literature in multiple individuals affected with glycogen storage disease type II, also known as Pompe disease (PMID: 18607768, 8558570, 17723315, 15121988, 19588081, 25752415, 24844452). This deletion is also known as c.2481+102_2646+31del (p.Gly828_Asn882del) in the literature. For these reasons, this variant has been classified as Pathogenic. |
| Laboratory for Molecular Medicine, |
RCV000813887 | SCV001652951 | pathogenic | Glycogen storage disease, type II | 2021-02-01 | criteria provided, single submitter | clinical testing | The deletion of exon 19 of GAA has been reported in the homozygous or compound heterozygous state in >20 individuals with glycogen storage disease II (GSDII; Kroos 1995 PMID:8558570, McCready 2007 PMID: 17723315, Joshi 2008 PMID: 18607768, Oba-Shinjo 2009 PMID: 19588081, Sacconi 2014 PMID:24844452, Pérez-López 2015 PMID:25752415). Of note, this variant is often reported as a deletion of exon 18 due to exon numbering differences. It has been identified in 0.013% (1/7624) of European chromosomes in gnomAD (http://gnomad.broadinstitute.org) and has been reported as Pathogenic in ClinVar (Variation ID 657307). This variant is predicted to result in the deletion of 55 amino acids (p.Gly828_Asn882del). Although it is not predicted to alter the protein reading-frame, the low frequency of this variant in the general population combined with its identification in multiple individuals with low or absent α-glucosidase activity strongly suggests that it is detrimental to protein function. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive GSDII. ACMG/AMP criteria applied: PM3_Very strong, PVS1_Moderate, PP4, PM2_Supporting. |
| Revvity Omics, |
RCV001784437 | SCV002023882 | pathogenic | not provided | 2023-07-31 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV000813887 | SCV004195500 | pathogenic | Glycogen storage disease, type II | 2024-02-13 | criteria provided, single submitter | clinical testing |