NM_000275.3(OCA2):c.1080C>T (p.Ser360=) AND Tyrosinase-positive oculocutaneous albinism

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Sep 4, 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:: RCV003128241.3

Allele description [Variation Report for NM_000275.3(OCA2):c.1080C>T (p.Ser360=)]

NM_000275.3(OCA2):c.1080C>T (p.Ser360=)

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.1080C>T (p.Ser360=)

HGVS:

NC_000015.10:g.27990612G>A
NG_009846.1:g.113701C>T
NM_000275.3:c.1080C>TMANE SELECT
NM_001300984.2:c.1045-946C>T
NP_000266.2:p.Ser360=
NC_000015.9:g.28235758G>A
NM_000275.2:c.1080C>T

Links:

dbSNP: rs373775562

NCBI 1000 Genomes Browser:

rs373775562

Molecular consequence:

NM_001300984.2:c.1045-946C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000275.3:c.1080C>T - synonymous variant - [Sequence Ontology: SO:0001819]

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
SCV000303416	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Sep 4, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003804576	Laboratoire de Génétique Moléculaire, CHU Bordeaux	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000303416

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Sep 4, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV003804576

Laboratoire de Génétique Moléculaire, CHU Bordeaux

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV000303416.2

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

Description

This variant has been reported in eight unrelated individuals, six of them in the compound heterozygous state, in a cohort study of oculocutaneous albinism (Michaud et al. 2023. PubMed ID: 37650133). While this variant is not predicted to affect splicing (SpliceAI, Jaganathan et al. 2019. PubMed ID: 30661751), a functional study using both a minigene splicing assay and RT-PCR analysis of patient blood samples demonstrated that the c.1080C>T variant increases the skipping of exon 10 in the transcript, which is predicted to result in a non-functional protein (Michaud et al. 2023. PubMed ID: 37650133). This variant is reported in 0.0040% of alleles in individuals of African descent in gnomAD. This variant is interpreted as likely 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 Laboratoire de Génétique Moléculaire, CHU Bordeaux, SCV003804576.1

#	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

Last Updated: Oct 26, 2024

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