OCA2 A481T - GET-Evidence

Curation:
Currentness:

OCA2 A481T

(OCA2 Ala481Thr)


Short summary

This variant is associated with lower melanin production and may result in less pigmentation in skin or eyes. The variant is suggested to play a role in oculocutaneous albinism when combined with more severe variants, but these findings lack statistical significance.

Variant evidence
Computational 1

Other variants in this gene cause oculocutaneous albinism

Functional 1

70% wildtype melanin production

See Sviderskaya EV et al. 1997 (8980282).

Case/Control

Findings lack statistical significance

See Lee ST et al. 1994 (8302318), Kawai M et al. 2005 (15942220).

Familial

No pedigree data

 
Clinical importance
Severity 3
Treatability 1
Penetrance 1

Hypothesized to cause a small increased chance of oculocutaneous albinism if combined with a severe variant

 

Impact

Low clinical importance, Uncertain pathogenic

(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

 

Allele frequency

  • T @ chr15:28228553: 0.1% (16/10758) in EVS
  • T @ chr15:25902147: 2.3% (3/128) in GET-Evidence
  • Frequency shown in summary reports: 0.1% (16/10758)

Publications
 

Lee ST, Nicholls RD, Bundey S, Laxova R, Musarella M, Spritz RA. Mutations of the P gene in oculocutaneous albinism, ocular albinism, and Prader-Willi syndrome plus albinism. N Engl J Med. 1994 Feb 24;330(8):529-34. PubMed PMID: 8302318.

This study examined this gene and the tyrosinase gene in four patients: three with type II oculocutaneous albinism, and one with a milder syndrome (autosomal recessive ocular albinism). This variant was seen compound heterozygous with a splice site mutation in the last case. It was seen heterozygously in 1 of 50 control individuals. These numbers (case+: 1, case-: 3, cont+: 1, cont-: 49) are not significant with a two-tailed Fisher’s exact test (p = 0.14).

Sviderskaya EV, Bennett DC, Ho L, Bailin T, Lee ST, Spritz RA. Complementation of hypopigmentation in p-mutant (pink-eyed dilution) mouse melanocytes by normal human P cDNA, and defective complementation by OCA2 mutant sequences. J Invest Dermatol. 1997 Jan;108(1):30-4. PubMed PMID: 8980282.

Expression studies show that the variant reduces protein levels to 70% of wildtype.

Kawai M, Suzuki T, Ito S, Inagaki K, Suzuki N, Tomita Y. A patient with subclinical oculocutaneous albinism type 2 diagnosed on getting severely sunburned. Dermatology. 2005;210(4):322-3. PubMed PMID: 15942220.

The variant is seen in a subclinical case of oculocutaneous albinism in a Japanese individual.

Duffy DL, Montgomery GW, Chen W, Zhao ZZ, Le L, James MR, Hayward NK, Martin NG, Sturm RA. A three-single-nucleotide polymorphism haplotype in intron 1 of OCA2 explains most human eye-color variation. Am J Hum Genet. 2007 Feb;80(2):241-52. Epub 2006 Dec 20. PubMed PMID: 17236130; PubMed Central PMCID: PMC1785344.

This variant is shown to be rare in the Caucasian population.

Yuasa I, Umetsu K, Harihara S, Miyoshi A, Saitou N, Park KS, Dashnyam B, Jin F, Lucotte G, Chattopadhyay PK, Henke L, Henke J. OCA2 481Thr, a hypofunctional allele in pigmentation, is characteristic of northeastern Asian populations. J Hum Genet. 2007;52(8):690-3. Epub 2007 Jun 14. PubMed PMID: 17568986.

This variant is shown to be common in the East Asian population.

Genomes
 

huE80E3D - CGI sample GS00253-DNA_D01_200_37
het T @ chr15:28228553

 

GS18942 - var-GS18942-1100-36-ASM
hom T @ chr15:25902148

 

Other external references
 

    dbSNP
  • rs74653330
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PolyPhen-2
  • Score: 0.961 (probably damaging)

Other in silico analyses
 

  • NBLOSUM100 score = 1
  • GET-Evidence autoscore = 6

Edit history
 

Gene search

"GENE" or "GENE A123C":

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