Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Serv. |
RCV003985700 | SCV004801339 | benign | Fabry disease | 2024-03-18 | criteria provided, single submitter | clinical testing | Fabry disease is an X-linked disorder due to mutations in GLA gene. This gene codifies for alpha-galactosidase. We found the c.311G>A (p.Gly104Asp) in the GLA gene in heterozygosity in a 10-year-old female with renal affectation. This variant could be classified as likely pathogenic if we apply the following criteria based on the ACMG guidelines: PP2, PP3, PM1, PM2, PM5. It is the rs869312274 in dbSNP. It is not reported in ClinVar nor in HGMD although there is a variant reported as pathogenic in the same base: c.311G>T (p.Gly104Val). We performed the alpha-galactosidase enzymatic activity in Dried Blood Spot (DBS) of the patient, and it was of 6.3 micromol/L.h (control range 4.7-18.8 micromol/L.h), so it was normal. As the alpha-galactosidase activity may be normal in affected women because of the different lyonization of the X-chromosome, her male relatives were requested. Her father and her paternal uncle healthy although they were hemizygous for the variant. We tested the alpha-galactosidase enzymatic activity in Dried Blood Spots (DBS) of both males and it was of 28 and 10 micromol/L.h respectively (control range 4.7-18.8 micromol/L.h), so they were absolutely normal. Taking into account that the father and the paternal uncle were carriers, that they both were healthy nowadays and that the alpha-galactosidase enzymatic activity tested in DBS was absolutely normal in both males, we consider this variant as BENIGN. The renal affectation of the index female was concluded not to be caused by Fabry disease. |