NM_000528.4(MAN2B1):c.590C>G (p.Pro197Arg) AND Deficiency of alpha-mannosidase

Clinical significance:Likely pathogenic (Last evaluated: Dec 27, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000207004.2

Allele description [Variation Report for NM_000528.4(MAN2B1):c.590C>G (p.Pro197Arg)]

NM_000528.4(MAN2B1):c.590C>G (p.Pro197Arg)

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.590C>G (p.Pro197Arg)
HGVS:
  • NC_000019.10:g.12664832G>C
  • NG_008318.1:g.6946C>G
  • NG_015814.1:g.3029G>C
  • NM_000528.4:c.590C>GMANE SELECT
  • NM_001173498.2:c.590C>G
  • NP_000519.2:p.Pro197Arg
  • NP_001166969.1:p.Pro197Arg
  • NC_000019.9:g.12775646G>C
  • NM_000528.3:c.590C>G
  • O00754:p.Pro197Arg
Protein change:
P197R
Links:
UniProtKB: O00754#VAR_068039; dbSNP: rs864621977
NCBI 1000 Genomes Browser:
rs864621977
Molecular consequence:
  • NM_000528.4:c.590C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001173498.2:c.590C>G - 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
SCV000243960ClinVar 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,

SCV000917601Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely pathogenic
(Dec 27, 2018)
germlineclinical testing

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

Citation Link

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

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

amamutdb.no: A relational database for MAN2B1 allelic variants that compiles genotypes, clinical phenotypes, and biochemical and structural data of mutant MAN2B1 in α-mannosidosis.

Riise Stensland HM, Frantzen G, Kuokkanen E, Buvang EK, Klenow HB, Heikinheimo P, Malm D, Nilssen Ø.

Hum Mutat. 2015 Jun;36(6):581-6. doi: 10.1002/humu.22787. Epub 2015 Apr 9.

PubMed [citation]
PMID:
25762455
See all PubMed Citations (3)

Details of each submission

From ClinVar Staff, National Center for Biotechnology Information (NCBI), SCV000243960.1

#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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000917601.1

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

Description

Variant summary: MAN2B1 c.590C>G (p.Pro197Arg) results in a non-conservative amino acid change located in the Glycoside hydrolase family 38, N-terminal domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 244732 control chromosomes. c.590C>G has been reported in the literature in an individual affected with Alpha-Mannosidosis (Borgwardt_2015). At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity in regards to intracellular processing and secretion into the medium in transfected cells, indicating an inactive protein (Kuokkanen_2011, Stensland_2015). 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 likely pathogenic.

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

Last Updated: Nov 27, 2021

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