USH2A V230M - GET-Evidence

Curation:
Currentness:

USH2A V230M

(USH2A Val230Met)


Short summary

This rare variant may be associated with Usher Syndrome II, but the literature seems to have concluded that it is a non-pathogenic polymorphism (including authors who earlier reported it as pathogenic).

Variant evidence
Computational 1

NBLOSUM < 3

Functional -
Case/Control 1

case/control data supports non-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

recessive

Summary of published research, and additional commentary

Case/control numbers are evaluated by counting chromosomes.

Total cases/controls case+ case– control+ control– p-value odds ratio
Usher Syndrome Type 2
6 678 3 387 1.0000 1.142

 

Allele frequency

  • T @ chr1:216538391: 1.6% (169/10758) in EVS
  • T @ chr1:214605013: 0.8% (1/128) in GET-Evidence
  • Frequency shown in summary reports: 1.6% (169/10758)

Publications
 

Dreyer B, Tranebjaerg L, Rosenberg T, Weston MD, Kimberling WJ, Nilssen O. Identification of novel USH2A mutations: implications for the structure of USH2A protein. Eur J Hum Genet. 2000 Jul;8(7):500-6. PubMed PMID: 10909849.

This variant was seen as a compound heterozygote (with the causative 2299delG) in a Caucasian individual with Usher syndrome type IIa (1 out of 31 patients screened). It was also seen in 1/100 control chromosomes. The variant is found in the N-terminus of the protein, but it is unclear what effect it could have on function.

Cases/controls case+ case– control+ control– p-value odds ratio
Usher Syndrome Type 2
1 61 1 99 1.0000 1.623

 

Leroy BP, Aragon-Martin JA, Weston MD, Bessant DA, Willis C, Webster AR, Bird AC, Kimberling WJ, Payne AM, Bhattacharya SS. Spectrum of mutations in USH2A in British patients with Usher syndrome type II. Exp Eye Res. 2001 May;72(5):503-9. PubMed PMID: 11311042.

This variant was seen heterozygously in one out of 36 families screened and not in 50 control individuals.

Cases/controls case+ case– control+ control– p-value odds ratio
Usher Syndrome Type 2
1 71 0 100 0.4186

 

Seyedahmadi BJ, Rivolta C, Keene JA, Berson EL, Dryja TP. Comprehensive screening of the USH2A gene in Usher syndrome type II and non-syndromic recessive retinitis pigmentosa. Exp Eye Res. 2004 Aug;79(2):167-73. PubMed PMID: 15325563.

The authors screened patients and controls and find this variant at similar frequencies in both groups: 4/275 patients and 2/95 controls (all heterozygous). They conclude it is a non-pathogenic polymorphism.

Cases/controls case+ case– control+ control– p-value odds ratio
Usher Syndrome Type 2
4 546 2 188 0.6499 0.689

 

Dreyer B, Brox V, Tranebjaerg L, Rosenberg T, Sadeghi AM, Möller C, Nilssen O. Spectrum of USH2A mutations in Scandinavian patients with Usher syndrome type II. Hum Mutat. 2008 Mar;29(3):451. PubMed PMID: 18273898.

The authors note that this mutation is rare but equally frequent in patients and controls. They conclude that it is non-pathogenic, reversing their earlier report of pathogenicity.

Genomes
 

 

hu4040B8 - CGI sample GS01175-DNA_D01 from PGP sample 31286272
het T @ chr1:216538391

 

huC30901 - CGI sample GS00253-DNA_B01_200_37
het T @ chr1:216538391

 

NA12878

 

Other external references
 

    dbSNP
  • rs45500891
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    GeneTests
  • GeneTests records for the USH2A gene
    Retinitis Pigmentosa, Autosomal Recessive
    Usher Syndrome Type 2
    USH2A-Related Retinitis Pigmentosa
    Usher Syndrome Type 2A
    www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/USH2A
    PolyPhen-2
  • Score: 0.006 (benign)
    Web search results (12 hits -- see all)
  • Development of a genotyping microarray for Usher syndrome ...
    The USH2A variant c.2299delG (p.E767fs) was previously described as a common ... The USH2A variant p.V230M was detected nine times in patients with all three ...
    jmg.bmj.com/content/44/2/153.full?rss=1
  • Development of a genotyping microarray for Usher syndrome
    for the heterozygous USH2A mutations in patients with USH1 ... The USH2A variant p.V230M was detected. nine times in patients with all three types of ...
    jmg.bmj.com/content/44/2/153.full.pdf+html
  • USH2A
    REFERENCES. USH2A. Usher Syndrome, Type 2A. R34X. 100C>T. exon 2. Norwegian (2) Dreyer 2000 ... Leroy 2001. V230M. 690G>A. exon 4. Danish (1); British (1) Dreyer 2000; ...
    hearing.harvard.edu/genepages/ush2adream.htm
  • USH2A SNPs - Genomewiki
    Usherin (USH2A), a 71-exon gene located on human chromosome 1q41] ... USH2A, while resembling a shuffle of ubiquitious domains, has potential ...
    genomewiki.ucsc.edu/index.php/USH2A_SNPs
  • Gendia | Microarray Testing
    gendia is an international network consisting of more than 100 laboratories. Gendia currently offers close to 2000 genetic tests.
    www.gendia.net/t18_note7.html
  • The molecular genetics of Usher syndrome
    (Omaha,NE) that markers at 1q41(USH2A)coseg- regate with the phenotype in many USH2 ... structure of usherin encoded by USH2A. There is a signal peptide ...
    ontogenez.narod.ru/pdfA/Usher.pdf
  • ush2a.xls
    (Number of families) REFERENCES. 2. USH2A. Usher Syndrome, Type 2A. R34X ... V230M. 690G>A. exon 4. Danish (1); British (1) Dreyer 2000; Leroy 2001. 8. L260X. 779T>G. exon 4 ...
    www.hpcgg.org/LMM/SeparatePages/ush2a.xls
  • Type III 95%
    ... (s) for variant Reference(s) for phosphorylation site TPSD1 Q9BZJ3 P15R 14 ... Polymorphism (dbSNP:rs3865205) 9920877 ST5 P78524 K316N 322 VAR_027101 STE20 (0. ...
    nih.go.kr/phosphovariant/html/family_whole/TypeIII_95.txt

Other in silico analyses
 

  • NBLOSUM100 score = 0
  • GET-Evidence autoscore = 3

Edit history
 

Gene search

"GENE" or "GENE A123C":

Log in