RAPSN R58C - GET-Evidence

Curation:
Currentness:

RAPSN R58C

(RAPSN Arg58Cys)


Short summary

Reported as non-pathogenic polymorphism.

Variant evidence
Computational -1

Polyphen 2 predicts damaging effect

Functional -
Case/Control 5

Allele frequency supports no significant pathogenic effect.

See Ohno K et al. 2002 (11791205).

Familial -
 
Clinical importance
Severity
Treatability -
Penetrance -
 

Impact

Low clinical importance, Uncertain benign

(The "low clinical importance, uncertain" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

unknown

Summary of published research, and additional commentary

If we were to compare the observations from (Ohno et al) to a hypothetical pathogenic variant, we find that this variant to be significantly benign (p < .0001) . This assumes that the variant is 100% penetrant and accounts for 100% of the disease. If these assumptions were not true, then the p value would be even lower.

Allele frequency

  • A @ chr11:47470345: 7.8% (837/10758) in EVS
  • A @ chr11:47426920: 4.7% (6/128) in GET-Evidence
  • Frequency shown in summary reports: 7.8% (837/10758)

Publications
 

Ohno K, Engel AG, Shen XM, Selcen D, Brengman J, Harper CM, Tsujino A, Milone M. Rapsyn mutations in humans cause endplate acetylcholine-receptor deficiency and myasthenic syndrome. Am J Hum Genet. 2002 Apr;70(4):875-85. Epub 2002 Jan 14. PubMed PMID: 11791205; PubMed Central PMCID: PMC379116.

These authors mention the variant as a polymorphism in their study, they treat it as having no significant pathogenic effect. They report an allele frequency of 9.9% (19/192).

Genomes
 

hu0E64A1 - CGI sample GS01173-DNA_B02 from PGP sample 94378523
het A @ chr11:47470345

 

 

 

hu44DCFF - CGI sample GS01669-DNA_C07 from PGP sample 74521372
het A @ chr11:47470345

 

hu7A4AD1 - CGI sample GS01669-DNA_C05 from PGP sample 42408046
het A @ chr11:47470345

 

hu9385BA - CGI sample GS00253-DNA_E01_200_37
het A @ chr11:47470345

 

huA0E089 - CGI sample GS01175-DNA_B04 from PGP sample 88590671
het A @ chr11:47470345

 

huAE4A11 - CGI sample GS01669-DNA_F02 from PGP sample 40767107
het A @ chr11:47470345

 

huBAAC98 - CGI sample GS01173-DNA_F02 from PGP sample 70008981
het A @ chr11:47470345

 

huBEDA0B

 

GS06985 - var-GS06985-1100-36-ASM
het A @ chr11:47426921

 

Other external references
 

    dbSNP
  • rs34312154
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    GeneTests
  • GeneTests records for the RAPSN gene
    Congenital Myasthenic Syndromes
    RAPSN-Related Congenital Myasthenic Syndrome
    RAPSN-Related Fetal Akinesia Deformation Sequence
    www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/RAPSN
    PolyPhen-2
  • Score: 0.995 (probably damaging)

Other in silico analyses
 

  • NBLOSUM100 score = 8
  • GET-Evidence autoscore = 4

Edit history
 

Gene search

"GENE" or "GENE A123C":

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