Submissions for variant NM_000528.4(MAN2B1):c.475G>A (p.Asp159Asn)

gnomAD frequency: 0.00001  dbSNP: rs864621976

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000206956	SCV000798920	uncertain significance	Deficiency of alpha-mannosidase	2018-03-28	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV005406919	SCV006072773	uncertain significance	not specified	2025-04-04	criteria provided, single submitter	clinical testing	Variant summary: MAN2B1 c.475G>A (p.Asp159Asn) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250968 control chromosomes. c.475G>A has been reported in the literature in an individual affected with Alpha-Mannosidosis (Riise_2012). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect (Kuokkanen_2011). The following publications have been ascertained in the context of this evaluation (PMID: 21505070, 22161967). ClinVar contains an entry for this variant (Variation ID: 208253). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
ClinVar Staff, National Center for Biotechnology Information (NCBI)	RCV000206956	SCV000243959	uncertain significance	Deficiency of alpha-mannosidase	2012-06-07	no assertion criteria provided	literature only