Submissions for variant NM_000528.4(MAN2B1):c.2355G>A (p.Thr785=)

dbSNP: rs1008745697

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000669668	SCV000794444	likely pathogenic	Deficiency of alpha-mannosidase	2017-09-27	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000669668	SCV000919601	pathogenic	Deficiency of alpha-mannosidase	2018-03-19	criteria provided, single submitter	clinical testing	Variant summary: MAN2B1 c.2355G>A (p.Thr785Thr) alters a conserved nucleotide located at the canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5 splicing donor site and three predict the variant creates a 3 acceptor site. At least one publication reports experimental evidence that this variant affects mRNA splicing (RiseStensland_2012). The variant allele was found at a frequency of 4.1e-06 in 245802 control chromosomes (gnomAD and publications). c.2355G>A has been reported in the literature in individuals affected with Alpha-Mannosidosis (both as compound heterozygotes and one homozygote)(RiseStensland_2012, Borgwardt_2015). These data indicate that the variant is likely to be associated with disease. 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.
Genome-Nilou Lab	RCV000669668	SCV002014109	likely pathogenic	Deficiency of alpha-mannosidase	2021-09-05	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000669668	SCV001454349	pathogenic	Deficiency of alpha-mannosidase	2020-09-16	no assertion criteria provided	clinical testing