NM_000528.4(MAN2B1):c.2140T>C (p.Trp714Arg) AND Deficiency of alpha-mannosidase

Clinical significance:Likely pathogenic (Last evaluated: Oct 12, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000206950.3

Allele description [Variation Report for NM_000528.4(MAN2B1):c.2140T>C (p.Trp714Arg)]

NM_000528.4(MAN2B1):c.2140T>C (p.Trp714Arg)

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_000528.4(MAN2B1):c.2140T>C (p.Trp714Arg)
HGVS:
  • NC_000019.10:g.12650129A>G
  • NG_008318.1:g.21649T>C
  • NM_000528.4:c.2140T>CMANE SELECT
  • NM_001173498.2:c.2137T>C
  • NP_000519.2:p.Trp714Arg
  • NP_001166969.1:p.Trp713Arg
  • NC_000019.9:g.12760943A>G
  • NM_000528.3:c.2140T>C
  • O00754:p.Trp714Arg
Protein change:
W713R
Links:
UniProtKB: O00754#VAR_003346; dbSNP: rs864621993
NCBI 1000 Genomes Browser:
rs864621993
Molecular consequence:
  • NM_000528.4:c.2140T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001173498.2:c.2137T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Deficiency of alpha-mannosidase (MANSA)
Synonyms:
Lysosomal alpha-D-mannosidase deficiency; Alpha mannosidase B deficiency; Mannosidosis, alpha B lysosomal; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009561; MedGen: C0024748; Orphanet: 61; OMIM: 248500

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000243993ClinVar Staff, National Center for Biotechnology Information (NCBI)no assertion criteria providedUncertain significance
(Jun 7, 2012)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Citation Link,

SCV001377537Invitaecriteria provided, single submitter
Likely pathogenic
(Oct 12, 2019)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedliterature only
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 (4)

Details of each submission

From ClinVar Staff, National Center for Biotechnology Information (NCBI), SCV000243993.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001377537.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces tryptophan with arginine at codon 714 of the MAN2B1 protein (p.Trp714Arg). The tryptophan residue is highly conserved and there is a moderate physicochemical difference between tryptophan and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with alpha-mannosidosis (PMID: 9915946, 22161967). ClinVar contains an entry for this variant (Variation ID: 208284). This variant has been reported to affect MAN2B1 protein function (PMID: 15035660). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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