NM_000275.3(OCA2):c.1465A>G (p.Asn489Asp) AND Tyrosinase-positive oculocutaneous albinism

Germline classification:: Pathogenic (6 submissions)
Last evaluated:: Nov 7, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000001012.20

Allele description [Variation Report for NM_000275.3(OCA2):c.1465A>G (p.Asn489Asp)]

NM_000275.3(OCA2):c.1465A>G (p.Asn489Asp)

Gene:

OCA2:OCA2 melanosomal transmembrane protein [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q13.1

Genomic location:

Preferred name:

NM_000275.3(OCA2):c.1465A>G (p.Asn489Asp)

HGVS:

NC_000015.10:g.27983383T>C
NG_009846.1:g.120930A>G
NM_000275.3:c.1465A>GMANE SELECT
NM_001300984.2:c.1393A>G
NP_000266.2:p.Asn489Asp
NP_001287913.1:p.Asn465Asp
NC_000015.9:g.28228529T>C
NM_000275.2:c.1465A>G
Q04671:p.Asn489Asp

Protein change:

N465D; ASN489ASP

Links:

UniProtKB: Q04671#VAR_006135; OMIM: 611409.0010; dbSNP: rs121918170

NCBI 1000 Genomes Browser:

rs121918170

Molecular consequence:

NM_000275.3:c.1465A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001300984.2:c.1393A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Tyrosinase-positive oculocutaneous albinism (OCA2)
Synonyms:: ALBINISM II; Albinism 2; Albinoidism; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008746; MedGen: C0268495; Orphanet: 79432; OMIM: 203200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000021162	OMIM	no assertion criteria provided	Pathogenic (Sep 1, 2003)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000596144	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 14, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000914660	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019)	Pathogenic (Oct 19, 2018)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 19060277, 24845642, 18326704, 12876664, 9259203 Citation Link,
SCV001760340	Genomics England Pilot Project, Genomics England	no assertion criteria provided (ACGS Guidelines, 2016)	Likely pathogenic	germline	clinical testing	Citation Link,
SCV002040586	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 7, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004099433	Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	no assertion criteria provided	Pathogenic (Oct 30, 2023)	germline	clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Birth prevalence and mutation spectrum in danish patients with autosomal recessive albinism.

Grønskov K, Ek J, Sand A, Scheller R, Bygum A, Brixen K, Brondum-Nielsen K, Rosenberg T.

Invest Ophthalmol Vis Sci. 2009 Mar;50(3):1058-64. doi: 10.1167/iovs.08-2639. Epub 2008 Dec 5.

PubMed [citation]

PMID:: 19060277

Relationship between foveal cone specialization and pit morphology in albinism.

Wilk MA, McAllister JT, Cooper RF, Dubis AM, Patitucci TN, Summerfelt P, Anderson JL, Stepien KE, Costakos DM, Connor TB Jr, Wirostko WJ, Chiang PW, Dubra A, Curcio CA, Brilliant MH, Summers CG, Carroll J.

Invest Ophthalmol Vis Sci. 2014 May 20;55(7):4186-98. doi: 10.1167/iovs.13-13217.

PubMed [citation]

PMID:: 24845642
PMCID:: PMC4098060

See all PubMed Citations (6)

Details of each submission

From OMIM, SCV000021162.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

For discussion of the asn489-to-asp (N489D) mutation in the OCA2 gene that was found in compound heterozygous state in a patient with oculocutaneous albinism type II (OCA2; 203200) by King et al. (2003), see 611409.0009.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genetic Services Laboratory, University of Chicago, SCV000596144.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Illumina Laboratory Services, Illumina, SCV000914660.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

The TCN2 c.497_498delTC (p.Leu166ProfsTer7) variant results in a frameshift, and is predicted to result in premature termination of the protein. The p.Leu166ProfsTer7 variant has been reported in two studies and is found in a total of four unrelated probands with transcobalamin II deficiency including three in a homozygous state and one in a compound heterozygous state (Schiff et al. 2010; Trakadis et al. 2014). Control data are unavailable for this variant, which is reported at a frequency of 0.00048 in the African population of the Exome Aggregation Consortium. Based on the evidence and the potential impact of frameshift variants, the p.Leu166ProfsTer7 variant is classified as pathogenic for transcobalamin II deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genomics England Pilot Project, Genomics England, SCV001760340.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome-Nilou Lab, SCV002040586.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Zotz-Klimas Genetics Lab, MVZ Zotz Klimas, SCV004099433.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 20, 2024

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