NM_000275.3(OCA2):c.1426A>G (p.Asn476Asp) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 16, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003553962.2

Allele description [Variation Report for NM_000275.3(OCA2):c.1426A>G (p.Asn476Asp)]

NM_000275.3(OCA2):c.1426A>G (p.Asn476Asp)

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.1426A>G (p.Asn476Asp)

HGVS:

NC_000015.10:g.27983422T>C
NG_009846.1:g.120891A>G
NG_009846.2:g.120893A>G
NG_130550.1:g.291T>C
NM_000275.3:c.1426A>GMANE SELECT
NM_001300984.2:c.1354A>G
NP_000266.2:p.Asn476Asp
NP_001287913.1:p.Asn452Asp
NC_000015.9:g.28228568T>C

Protein change:

N452D

Molecular consequence:

NM_000275.3:c.1426A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001300984.2:c.1354A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004296563	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 16, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 17385796, 31077556, 32552135, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004296563

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 16, 2024)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Prenatal diagnosis of oculocutaneous albinism type II and novel mutations in two Chinese families.

Hongyi L, Haiyun W, Hui Z, Qing W, Honglei D, Shu M, Weiying J.

Prenat Diagn. 2007 Jun;27(6):502-6.

PubMed [citation]

PMID:: 17385796

Comprehensive analysis of spectral distribution of a large cohort of Chinese patients with non-syndromic oculocutaneous albinism facilitates genetic diagnosis.

Zhong Z, Gu L, Zheng X, Ma N, Wu Z, Duan J, Zhang J, Chen J.

Pigment Cell Melanoma Res. 2019 Sep;32(5):672-686. doi: 10.1111/pcmr.12790. Epub 2019 May 29.

PubMed [citation]

PMID:: 31077556
PMCID:: PMC6852118

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004296563.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 476 of the OCA2 protein (p.Asn476Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with ocular albinism (PMID: 17385796, 31077556, 32552135). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae 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

Last Updated: Sep 29, 2024

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