NM_000528.4(MAN2B1):c.1351G>T (p.Gly451Cys) AND Deficiency of alpha-mannosidase

Clinical significance:Pathogenic (Last evaluated: Sep 5, 2021)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000206900.4

Allele description [Variation Report for NM_000528.4(MAN2B1):c.1351G>T (p.Gly451Cys)]

NM_000528.4(MAN2B1):c.1351G>T (p.Gly451Cys)

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.1351G>T (p.Gly451Cys)
HGVS:
  • NC_000019.10:g.12657514C>A
  • NG_008318.1:g.14264G>T
  • NM_000528.4:c.1351G>TMANE SELECT
  • NM_001173498.2:c.1348G>T
  • NP_000519.2:p.Gly451Cys
  • NP_001166969.1:p.Gly450Cys
  • NC_000019.9:g.12768328C>A
  • NM_000528.3:c.1351G>T
  • O00754:p.Gly451Cys
Protein change:
G450C
Links:
UniProtKB: O00754#VAR_068053; dbSNP: rs368899357
NCBI 1000 Genomes Browser:
rs368899357
Molecular consequence:
  • NM_000528.4:c.1351G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001173498.2:c.1348G>T - 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
SCV000243972ClinVar 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,

SCV001390765Invitaecriteria provided, single submitter
Pathogenic
(Sep 15, 2020)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV002014387Nilou-Genome Labcriteria provided, single submitter
Pathogenic
(Sep 5, 2021)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedliterature only
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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

Molecular and cellular characterization of novel {alpha}-mannosidosis mutations.

Kuokkanen E, Riise Stensland HM, Smith W, Kjeldsen Buvang E, Van Nguyen L, Nilssen Ø, Heikinheimo P.

Hum Mol Genet. 2011 Jul 1;20(13):2651-61. doi: 10.1093/hmg/ddr167. Epub 2011 Apr 19.

PubMed [citation]
PMID:
21505070
See all PubMed Citations (4)

Details of each submission

From ClinVar Staff, National Center for Biotechnology Information (NCBI), SCV000243972.1

#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, SCV001390765.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces glycine with cysteine at codon 451 of the MAN2B1 protein (p.Gly451Cys). The glycine residue is highly conserved and there is a large physicochemical difference between glycine and cysteine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in individual(s) with mannosidosis (PMID: 22161967). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 208266). This variant has been reported to affect MAN2B1 protein function (PMID: 22161967, 21505070). For these reasons, this variant has been classified as Pathogenic.

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

From Nilou-Genome Lab, SCV002014387.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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