Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002238562 | SCV002511455 | pathogenic | Mucopolysaccharidosis, MPS-III-B | 2022-04-05 | criteria provided, single submitter | clinical testing | Variant summary: NAGLU c.678+1G>A alters a conserved nucleotide 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 the canonical 5' splicing donor site. At least one publication reports experimental evidence that this variant affects mRNA splicing resulting in complete skipping of exon 3 as well as a population that results in skipping of both exons 2 and 3 (example, Tessitore_2000). The variant was absent in 249398 control chromosomes. c.678+1G>A has been reported in the literature in individuals affected with Mucopolysaccharidosis Type IIIB (Sanfilippo Syndrome B) (example, Tessitore_2000). These data do not allow any conclusion about variant significance. 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 pathogenic. |