MBL2 R52C - GET-Evidence

Note: This variant has not been sufficiently evaluated by a GET-Evidence editor.

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Curation:
Currentness:

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MBL2 R52C

(MBL2 Arg52Cys)


You are viewing an old version of this page that was saved on February 28, 2010 at 12:45pm by Madeleine Ball.

Short summary

This variant is associated with mannose binding protein deficiency which leads to impaired complement system immune response to mannose-rich pathogens. Patients homozygous for this allele or compound heterozygous are likely to have increased susceptibility to infection. The wild-type version of this gene is known as variant allele A, while this is called variant allele D. See G54D (variant B) and G57E (variant C).

Variant evidence
Computational 2

Other mutations in the gene are associated with mannose binding protein deficiency, NBLOSUM = 5.

See unpublished research (below).

Functional -
Case/Control 3

OR = 6.3, significance = 0.0005.

See Garred P et al. 1995 (7564730), Hibberd ML et al. 1999 (10199352), unpublished research (below).

Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Insufficiently evaluated pathogenic

(The "insufficiently evaluated" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

recessive

Summary of published research, and additional commentary

 

Total cases/controls case+ case– control+ control– p-value odds ratio
Mannose-Binding Lectin Deficiency
18 477 3 502 0.0007 6.314

 

Allele frequency

  • A @ chr10:54531242: 4.9% (523/10758) in EVS
  • A @ chr10:54201247: 4.0% (5/126) in GET-Evidence
  • Frequency shown in summary reports: 4.9% (523/10758)

Publications
 

Garred P, Madsen HO, Hofmann B, Svejgaard A. Increased frequency of homozygosity of abnormal mannan-binding-protein alleles in patients with suspected immunodeficiency. Lancet. 1995 Oct 7;346(8980):941-3. PubMed PMID: 7564730.

A study of patients with suspected immunodeficiency found a higher number of homozygous and compound heterozygous patients with abnormal mannan-binding protein (MBP) alleles (variants B, C, and D). In the case group of 229 patients, one patient was homozygous for D and five were compound heterozygous for B/D. No patients in the control population of 123 controls were homozygous or compound heterozygous for this allele.

Cases/controls case+ case– control+ control– p-value odds ratio
Mannose-Binding Lectin Deficiency
6 223 0 123 0.0953

 

Hibberd ML, Sumiya M, Summerfield JA, Booy R, Levin M. Association of variants of the gene for mannose-binding lectin with susceptibility to meningococcal disease. Meningococcal Research Group. Lancet. 1999 Mar 27;353(9158):1049-53. PubMed PMID: 10199352.

A study of the frequency of MBL2 variants was made comparing children meningococcal disease with controls. Of 266 patients, none were homozygous for R52C and 12 were compound heterozygous for R52C and either G54D or G57E. Of 382 controls, 3 were compound heterozygous for R52C.

Cases/controls case+ case– control+ control– p-value odds ratio
Mannose-Binding Lectin Deficiency
12 254 3 379 0.0026 5.969

 

Added in this revision:

Hellemann D, Larsson A, Madsen HO, Bonde J, Jarløv JO, Wiis J, Faber T, Wetterslev J, Garred P. Heterozygosity of mannose-binding lectin (MBL2) genotypes predicts advantage (heterosis) in relation to fatal outcome in intensive care patients. Hum Mol Genet. 2007 Dec 15;16(24):3071-80. Epub 2007 Sep 14. PubMed PMID: 17872904.

 

Genomes
 

hu04FD18 - CGI sample GS00253-DNA_F01_200_37
het A @ chr10:54531242

 

huE80E3D - CGI sample GS00253-DNA_D01_200_37
het A @ chr10:54531242

 

snp-6

 

Other external references
 

    dbSNP
  • rs5030737
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PolyPhen-2
  • Score: 0.999 (probably damaging)

Other in silico analyses
 

  • NBLOSUM100 score = 8
  • GET-Evidence autoscore = 5

Edit history
 

Gene search

"GENE" or "GENE A123C":

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