Submissions for variant NM_000157.4(GBA1):c.1599G>A (p.Trp533Ter)

dbSNP: rs1671655923

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003317439	SCV004020750	pathogenic	Gaucher disease	2023-06-15	criteria provided, single submitter	clinical testing	Variant summary: GBA c.1599G>A (p.Trp533X) results in a premature termination codon. While the variant is not expected to undergo nonsense-mediated decay, variants downstream of this position have been classified as pathogenic by our laboratory (p.Arg535Cys, p.Arg535His). The variant was absent in 176860 control chromosomes. c.1599G>A has been reported in the literature in compound heterozygous indivudals affected with Gaucher Disease including one neonatal case who carried a VUS in cis and a pathogenic variant in trans (Phetthong_2021, Lecourt_2013). At least one publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect (Lecourt_2013). The following publications have been ascertained in the context of this evaluation (PMID: 23935976, 34930372). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Department of Pediatrics, Division of Medical Genetics, Faculty of Medicine Ramathibodi Hospital, Mahidol University	RCV001175136	SCV001334297	pathogenic	Gaucher disease type I	2020-06-04	no assertion criteria provided	research	The c.1599G>A variant in GBA was absent from large population and our in-house database. This variant segregated with the non-neuronopathic Gaucher disease. The glucocerbrosidase enzyme activity was deficient.