NM_000528.4(MAN2B1):c.1055T>C (p.Leu352Pro) AND Deficiency of alpha-mannosidase

Clinical significance:Likely pathogenic (Last evaluated: May 15, 2019)

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:
RCV000206932.4

Allele description [Variation Report for NM_000528.4(MAN2B1):c.1055T>C (p.Leu352Pro)]

NM_000528.4(MAN2B1):c.1055T>C (p.Leu352Pro)

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.1055T>C (p.Leu352Pro)
HGVS:
  • NC_000019.10:g.12658482A>G
  • NG_008318.1:g.13296T>C
  • NM_000528.4:c.1055T>CMANE SELECT
  • NM_001173498.2:c.1052T>C
  • NP_000519.2:p.Leu352Pro
  • NP_001166969.1:p.Leu351Pro
  • NC_000019.9:g.12769296A>G
  • NM_000528.3:c.1055T>C
  • O00754:p.Leu352Pro
Protein change:
L351P
Links:
UniProtKB: O00754#VAR_068048; dbSNP: rs864621980
NCBI 1000 Genomes Browser:
rs864621980
Molecular consequence:
  • NM_000528.4:c.1055T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001173498.2:c.1052T>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

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
SCV000243967ClinVar 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,

SCV001395540Invitaecriteria provided, single submitter
Likely pathogenic
(May 15, 2019)
germlineclinical testing

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

SCV001437578Department of Medical Genetics, Oslo University Hospitalcriteria provided, single submitter
Likely pathogenicgermlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot providednot providednot providedclinical testing, literature 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), SCV000243967.1

#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, SCV001395540.2

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

Description

This sequence change replaces leucine with proline at codon 352 of the MAN2B1 protein (p.Leu352Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with mannosidosis in a family (PMID: 22161967). ClinVar contains an entry for this variant (Variation ID: 208261). This variant has been reported to affect MAN2B1 protein function (PMID: 22161967, 21505070). 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

From Department of Medical Genetics, Oslo University Hospital, SCV001437578.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Oct 30, 2021

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