Submissions for variant NM_000046.5(ARSB):c.312+2T>G

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	RCV003230896	SCV003928869	likely pathogenic	Mucopolysaccharidosis type 6	2023-04-06	criteria provided, single submitter	clinical testing	Variant summary: ARSB c.312+2T>G 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 canonical 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 71310 control chromosomes (gnomAD). c.312+2T>G has been reported in the literature in at least one compound heterozygous individual affected with Mucopolysaccharidosis Type VI (Maroteaux-Lamy Syndrome, Fang_2022). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Baylor Genetics	RCV003230896	SCV004206727	pathogenic	Mucopolysaccharidosis type 6	2023-10-07	criteria provided, single submitter	clinical testing