FLG H2463D - GET-Evidence

Curation:
Currentness:

FLG H2463D

(FLG His2463Asp)


Short summary

Tentatively evaluated as benign. Other, much more severe null mutations cause increased susceptibility ichthyosis vulgaris, atopic eczema, and allergies.

Variant evidence
Computational

Polyphen 2 predicts damaging effect, but pathogenic effects are associated with more severe null mutants (nonsense and frameshift mutations)

Functional -
Case/Control

No data for this variant

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

Other more severe variants null mutations including R501X, 2282del4, and 3702delG (which have a combined allele frequency of around 5% in Europeans) are associated with causing ichthyosis vulgaris, atopic eczema, hay fever, and asthma. E.g. http://www.nature.com/jid/journal/v127/n3/full/5700587a.html

Because this variant is a substitution rather than a null mutation, and we have no known reports of FLG substitutions being pathogenic, it is tentatively evaluated as benign.

Allele frequency

  • C @ chr1:152279975: 0.7% (70/10758) in EVS
  • C @ chr1:150546598: 0.8% (1/128) in GET-Evidence
  • Frequency shown in summary reports: 0.7% (70/10758)

Publications
 

Genomes
 

huBEDA0B - CGI sample GS00253-DNA_C01_200_37
het C @ chr1:152279975

 

Other external references
 

    dbSNP
  • rs113188294
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    GeneTests
  • GeneTests records for the FLG gene
    FGFR-Related Craniosynostosis
    Kallmann Syndrome
    FGFR1-Related Craniosynostosis
    Kallmann Syndrome 2
    Osteoglophonic Dysplasia
    Pfeiffer Syndrome Type 1, 2 and 3
    Ichthyosis Vulgaris
    www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/FLG
    PolyPhen-2
  • Score: 0.998 (probably damaging)

Other in silico analyses
 

  • NBLOSUM100 score = 3
  • GET-Evidence autoscore = 4

Edit history
 

Gene search

"GENE" or "GENE A123C":

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