Submissions for variant NM_000528.4(MAN2B1):c.1645-2A>T

gnomAD frequency: 0.00001  dbSNP: rs891030696

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000674925	SCV000800341	likely pathogenic	Deficiency of alpha-mannosidase	2018-06-04	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000674925	SCV003844583	likely pathogenic	Deficiency of alpha-mannosidase	2023-02-02	criteria provided, single submitter	clinical testing	Variant summary: MAN2B1 c.1645-2A>T 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: Three predict the variant abolishes the canonical 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 249896 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1645-2A>T in individuals affected with Alpha-Mannosidosis and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.