NM_000275.3(OCA2):c.1239+5G>C AND not specified

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 15, 2023
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:: RCV001818417.6

Allele description [Variation Report for NM_000275.3(OCA2):c.1239+5G>C]

NM_000275.3(OCA2):c.1239+5G>C

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.1239+5G>C

HGVS:

NC_000015.10:g.27986582C>G
NG_009846.1:g.117731G>C
NM_000275.3:c.1239+5G>CMANE SELECT
NM_001300984.2:c.1167+5G>C
NC_000015.9:g.28231728C>G
NM_000275.2:c.1239+5G>C

Links:

dbSNP: rs757119713

NCBI 1000 Genomes Browser:

rs757119713

Molecular consequence:

NM_000275.3:c.1239+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001300984.2:c.1167+5G>C - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002069185	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 8, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004241537	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Dec 15, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002069185

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jun 8, 2018)

germline

clinical testing

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

SCV004241537

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Dec 15, 2023)

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	no	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 Genetic Services Laboratory, University of Chicago, SCV002069185.1

#	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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004241537.1

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

Description

Variant summary: OCA2 c.1239+5G>C alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Two predict the variant weakens the canonical 5' donor site and three predict the variant abolishes a downstream cryptic 5' donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 251376 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1239+5G>C in individuals affected with Oculocutaneous Albinism and no experimental evidence demonstrating its impact on protein function have been reported in the literature. Five submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Three submitters classified the variant as uncertain significance and two submitters, one citing internal data, classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as uncertain significance.

#	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: Oct 8, 2024

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