VCAN T689A - GET-Evidence

Curation:
Currentness:

VCAN T689A

(VCAN Thr689Ala)


Short summary

Probably not pathogenic, seen in two healthy PGP participants, contradicting a severe pathogenic effect.

Variant evidence
Computational -1

Polyphen 2 predicts damaging effect

Functional -
Case/Control 4

Seen in two healthy PGP participants, strongly contradicting a severe dominant pathogenic effect

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

This variant was seen in two out of 128 random, presumed-healthy alleles. Although Polyphen 2 predicts the variant to be disruptive and this gene has been implicated in causing Wagner syndrome when disrupted (vitreoretinopathy), this is a very rare disorder (less than 50 families reported according to GeneTests Feb 2009 article) and is autosomal dominant. The variant is seen in two PGP participants who have not reported this condition, strongly contradicting it having this severe, dominant pathogenic effect.

Allele frequency

  • G @ chr5:82816190: 0.6% (69/10712) in EVS
  • G @ chr5:82851945: 1.6% (2/128) in GET-Evidence
  • Frequency shown in summary reports: 0.6% (69/10712)

Publications
 

Genomes
 

hu04FD18 - CGI sample GS00253-DNA_F01_200_37
het G @ chr5:82816190

 

 

 

huAE6220 - CGI sample GS00253-DNA_H01_200_37
het G @ chr5:82816190

 

Other external references
 

    dbSNP
  • rs61754531
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PolyPhen-2
  • Score: 0.862 (probably damaging)
    Web search results (0 hits -- see all)

Other in silico analyses
 

  • NBLOSUM100 score = 1
  • GET-Evidence autoscore = 4

Edit history
 

Gene search

"GENE" or "GENE A123C":

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