NM_000275.3(OCA2):c.1349C>T (p.Thr450Met) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Sep 30, 2024
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:: RCV001583207.28

Allele description [Variation Report for NM_000275.3(OCA2):c.1349C>T (p.Thr450Met)]

NM_000275.3(OCA2):c.1349C>T (p.Thr450Met)

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.1349C>T (p.Thr450Met)

HGVS:

NC_000015.10:g.27985079G>A
NG_009846.1:g.119234C>T
NM_000275.3:c.1349C>TMANE SELECT
NM_001300984.2:c.1277C>T
NP_000266.2:p.Thr450Met
NP_001287913.1:p.Thr426Met
NC_000015.9:g.28230225G>A
NM_000275.2:c.1349C>T

Protein change:

T426M

Links:

dbSNP: rs772019064

NCBI 1000 Genomes Browser:

rs772019064

Molecular consequence:

NM_000275.3:c.1349C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001300984.2:c.1277C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001810835	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Sep 30, 2024)	germline	clinical testing	Citation Link,
SCV002232220	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 10, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 26165494, 28976636, 31077556, 31813138, 28492532
SCV002822167	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Oct 1, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001810835

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Sep 30, 2024)

germline

clinical testing

Citation Link,

SCV002232220

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 10, 2024)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV002822167

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Oct 1, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Prenatal genotyping of four common oculocutaneous albinism genes in 51 Chinese families.

Wei AH, Zang DJ, Zhang Z, Yang XM, Li W.

J Genet Genomics. 2015 Jun 20;42(6):279-86. doi: 10.1016/j.jgg.2015.05.001. Epub 2015 May 29.

PubMed [citation]

PMID:: 26165494

Lessons of a day hospital: Comprehensive assessment of patients with albinism in a European setting.

Marti A, Lasseaux E, Ezzedine K, Léauté-Labrèze C, Boralevi F, Paya C, Coste V, Deroissart V, Arveiler B, Taieb A, Morice-Picard F.

Pigment Cell Melanoma Res. 2018 Mar;31(2):318-329. doi: 10.1111/pcmr.12651. Epub 2017 Oct 21.

PubMed [citation]

PMID:: 28976636

See all PubMed Citations (5)

Details of each submission

From GeneDx, SCV001810835.3

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

Description

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 18683130, 26165494, 28976636, 31077556, 21458243, 35488210, 31196117, 34838614, 18821858, 29437493, 37471664, 31813138)

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002232220.4

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

Description

This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 450 of the OCA2 protein (p.Thr450Met). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with oculocutaneous albinism (PMID: 26165494, 28976636, 31077556, 31813138). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1211398). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt OCA2 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.

#	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 CeGaT Center for Human Genetics Tuebingen, SCV002822167.16

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

Description

OCA2: PM3:Very Strong, PM2, PM5, PP3

#	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		1	not provided	not provided	not provided

Last Updated: Apr 7, 2025

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