NM_000528.3(MAN2B1):c.2248C>T (p.Arg750Trp) AND Deficiency of alpha-mannosidase

This record was updated by the submitter. Please see the current version.

Germline classification:: Conflicting classifications of pathogenicity (4 submissions)
Last evaluated:: Nov 24, 2015
Review status:: criteria provided, conflicting classifications

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000001755.5

Allele description

NM_000528.3(MAN2B1):c.2248C>T (p.Arg750Trp)

Gene:

MAN2B1:mannosidase alpha class 2B member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.13

Genomic location:

Preferred name:

NM_000528.3(MAN2B1):c.2248C>T (p.Arg750Trp)

HGVS:

NC_000019.10:g.12649932G>A
NG_008318.1:g.21846C>T
NM_000528.3:c.2248C>T
NP_000519.2:p.Arg750Trp
NC_000019.9:g.12760746G>A
NM_000528.2:c.2248C>T
O00754:p.Arg750Trp

Protein change:

R750W; ARG750TRP

Links:

UniProtKB: O00754#VAR_003347; OMIM: 609458.0004; dbSNP: rs80338680

GMAF:

0.0002(A), 80338680

NCBI 1000 Genomes Browser:

rs80338680

Allele Frequency:

0.0002, GO-ESP

Molecular consequence:

NM_000528.3:c.2248C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Deficiency of alpha-mannosidase (MANSA)
Synonyms:: Alpha-Mannosidosis
Identifiers:: MedGen: C0024748; Orphanet: 61; OMIM: 248500
Age of onset:: Childhood
Prevalence:: 1-9 / 1 000 000 61

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000021911	OMIM	no assertion criteria provided	Pathogenic (Mar 1, 2012)	germline	literature only	PubMed (3) [See all records that cite these PMIDs] 9758606, 9915946, 22161967
SCV000040754	GeneReviews	no assertion criteria provided	pathologic (May 3, 2012)	not provided	curation
SCV000243990	ClinVar Staff, National Center for Biotechnology Information (NCBI)	no assertion criteria provided	Uncertain significance (Jun 7, 2012)	germline	literature only	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV000485236	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Pathogenic (Nov 24, 2015)	unknown	clinical testing	mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf Citation Link

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	not provided	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Spectrum of mutations in alpha-mannosidosis.

Berg T, Riise HM, Hansen GM, Malm D, Tranebjaerg L, Tollersrud OK, Nilssen O.

Am J Hum Genet. 1999 Jan;64(1):77-88.

PubMed [citation]

PMID:: 9915946
PMCID:: PMC1377705

Identification of 83 novel alpha-mannosidosis-associated sequence variants: functional analysis of MAN2B1 missense mutations.

Riise Stensland HM, Klenow HB, Van Nguyen L, Hansen GM, Malm D, Nilssen Ø.

Hum Mutat. 2012 Mar;33(3):511-20. doi: 10.1002/humu.22005. Epub 2012 Jan 23. Erratum in: Hum Mutat. 2016 Aug;37(8):827.

PubMed [citation]

PMID:: 22161967

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000021911.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (3)

Description

For discussion of the arg750-to-trp (R750W) mutation in the MAN2B1 gene that was found in compound heterozygous state in a patient with alpha-mannosidosis (MANSA; 248500) by Gotoda et al. (1998), see 609458.0003.

Berg et al. (1999) identified the arg750-to-trp (R750W) mutation in 13 patients with alpha-mannosidosis from different European countries. R750W accounted for 21% of disease alleles.

Riise Stensland et al. (2012) identified the R750W mutation in 50 of 130 unrelated patients with alpha-mannosidosis from 30 countries. It was the most common mutation, accounting for 27.3% of disease alleles. Haplotype analysis indicated at least 4 independent events causing R750W, with 1 haplotype accounting for 95% of the alleles. Population-based analysis suggested that the mutant allele arose in eastern Europe. The mutation was found in patients with mild, moderate, and severe disease.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneReviews, SCV000040754.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	not provided	not provided	not provided	not provided	Assert pathogenicity		not provided	not provided	not provided	not provided

From ClinVar Staff, National Center for Biotechnology Information (NCBI), SCV000243990.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Counsyl, SCV000485236.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Aug 13, 2017

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