OCA2 R305W - GET-Evidence

Curation:
Currentness:

OCA2 R305W

(OCA2 Arg305Trp)


Short summary

This variant is associated with eye color, as is OCA2 Arg419Gln. Individuals with this variant are more likely to have brown/black eyes (as opposed to blue/gray or green/hazel). Other variants in this gene are associated with oculocutaneous albinism (albinism which involves skin and eyes).

Variant evidence
Computational 2

Gene is associated with pigmentation, BLOSUM score suggests disruptive amino acid change.

Functional -
Case/Control 4

p < 0.001

See Rebbeck TR et al. 2002 (12163334), Jannot AS et al. 2005 (15889046).

Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Low clinical importance, Likely benign

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

Inheritance pattern

unknown

Summary of published research, and additional commentary

 

Allele frequency

  • A @ chr15:28260053: 8.2% (877/10758) in EVS
  • A @ chr15:25933647: 9.4% (12/128) in GET-Evidence
  • Frequency shown in summary reports: 8.2% (877/10758)

Publications
 

Rebbeck TR, Kanetsky PA, Walker AH, Holmes R, Halpern AC, Schuchter LM, Elder DE, Guerry D. P gene as an inherited biomarker of human eye color. Cancer Epidemiol Biomarkers Prev. 2002 Aug;11(8):782-4. PubMed PMID: 12163334.

This allele is associated with brown/black eyes vs. blue/gray and green/hazel eyes. 9.8% and 11.8% of individuals with blue/gray or green/hazel eyes have one or two copies of this variant, while 21.4% of individuals with brown/black eyes have one or two copies. P value < 0.001 and the highest odds ratio (blue/gray vs brown/black) was 2.48. They also report an association with Arg419Gln and green/hazel eyes vs. blue/gray.

Jannot AS, Meziani R, Bertrand G, Gérard B, Descamps V, Archimbaud A, Picard C, Ollivaud L, Basset-Seguin N, Kerob D, Lanternier G, Lebbe C, Saiag P, Crickx B, Clerget-Darpoux F, Grandchamp B, Soufir N, Melan-Cohort. Allele variations in the OCA2 gene (pink-eyed-dilution locus) are associated with genetic susceptibility to melanoma. Eur J Hum Genet. 2005 Aug;13(8):913-20. PubMed PMID: 15889046.

This study looked for and found association of malignant melanoma with variants in OCA2, and this association remains even when other risk factors are taken into account (skin color, eye color, nevus count, etc). This variant did not, however, show any association with malignant melanoma. They confirm that this variant (which they call SNP 5) is associated with dark eye color (p = 0.007). (They do not report a significant association for Arg419Gly, probably because they classified eyes as dark or light, combining both green and blue into a single category.)

Genomes
 

hu025CEA - CGI sample GS01669-DNA_D02 from PGP sample 27316983
het A @ chr15:28260053

 

hu4339C0 - CGI sample GS01175-DNA_H01 from PGP sample 94797469
het A @ chr15:28260053

 

hu9385BA - CGI sample GS00253-DNA_E01_200_37
het A @ chr15:28260053

 

huBAAC98 - CGI sample GS01173-DNA_F02 from PGP sample 70008981
het A @ chr15:28260053

 

huE80E3D - CGI sample GS00253-DNA_D01_200_37
het A @ chr15:28260053

 

GS18508 - var-GS18508-1100-36-ASM
het A @ chr15:25933648

 

GS19238 - var-GS19238-1100-36-ASM
het A @ chr15:25933648

 

GS19240 - var-GS19240-1100-36-ASM
het A @ chr15:25933648

 

GS20502 - var-GS20502-1100-36-ASM
het A @ chr15:25933648

 

Other external references
 

    dbSNP
  • rs1800401
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PolyPhen-2
  • Score: 0.961 (probably damaging)
    Web search results (28 hits -- see all)
  • Re-identification
    However, it will be very hard for anyone to learn anything about you personally from any of this research ... OcculoCut.Albinism OCA2 15 q11.2-q12 * R305W, R419Q blue to brown ...
    arep.med.harvard.edu/PGP/Anon.htm
  • OMIM: 611409
    MIM Entry: 611409 Title: *611409 OCA2 GENE ;;PINK-EYED DILUTION; PED;; P GENE ... the association of the R305W variant in OCA2 with nonblue eye color ...
    www.genome.jp/dbget-bin/www_bget?omim+611409
  • Interactive effects of MC1R and OCA2 on melanoma risk phenotypes
    To assess the interaction of the brown eye color gene OCA2 on the ... This is probably due to the association of these OCA2 SNPs with brown/green not ...
    hmg.oxfordjournals.org/cgi/reprint/13/4/447.pdf
  • Eye colour: portals into pigmentation genes and ancestry
    variant alleles of OCA2 have been identified: 24 of which. are exonic ... found two of these OCA2 coding- region variants, R305W and R419Q were associated with ...
    biosci.ohio-state.edu/.../eeobmg640/reading1eyecolor.pdf
  • BioMed Central | Full text | Genetic determinants of hair and ...
    We found replicable associations of hair colour with the KITLG and OCA2 genes. ... However, the OCA2 coding SNPs R419Q (rs1800407) and R305W (rs1800401) were not ...
    www.biomedcentral.com/1471-2156/10/88
  • A Genome Scan for Eye Color in 502 Twin Families: Most ...
    telomeric of OCA2 and inflating the QTL estimate. No other peaks ... With two OCA2 coding region vari- ants, R305W and R419Q, shown to be associated. with non ...
    genepi.qimr.edu.au/contents/p/staff/CV373.pdf
  • BMC Genetics
    However, the OCA2 coding SNPs R419Q (rs1800407) and R305W (rs1800401) were not ... The OCA2 gene was first identified in mice, in which. mutations of the ...
    www.biomedcentral.com/content/pdf/1471-2156-10-88.pdf
  • Oculocutaneous albinism type 2 (OCA2) with homozygous 2.7-kb ...
    locutaneous albinism type 2 (OCA2) patients homozygous. for the 2.7-kb ... Exon 9 R305W A/G intron 13 pos +26 A/G intron 13 pos +113 T/C Exon 22 A776A T/C intron 22 ...
    ese.u-psud.fr/bases/upresa/pages/.../Aquaron_2007_JHG.pdf
  • Novel and recurrent mutations in the tyrosinase gene and the ...
    all clinical diagnoses of OCA2 are indeed caused by mu- tations in the tyrosinase gene ... changes (R305W, R419Q), whereas the remaining ones. were silent (Table ...
    www.albinismus.info/literatur/AlbiPuibmitWeber.pdf

Other in silico analyses
 

  • NBLOSUM100 score = 7
  • GET-Evidence autoscore = 5

Edit history
 

Gene search

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