Submissions for variant NM_020944.3(GBA2):c.451+1G>A

dbSNP: rs769002624

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001280667	SCV001467959	likely pathogenic	Hereditary spastic paraplegia 46	2020-12-17	criteria provided, single submitter	clinical testing	Variant summary: GBA2 c.451+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 251436 control chromosomes (gnomAD). To our knowledge, no occurrence of c.451+1G>A in individuals affected with Spastic Paraplegia 46, Autosomal Recessive and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Other splice-site variants in GBA2 gene have been reported in online databases (HGMD) to be associated with disease. Based on the evidence outlined above, the variant was classified as likely pathogenic.