NM_000275.3(OCA2):c.2338+1G>T AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 10, 2023
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:: RCV001950284.4

Allele description [Variation Report for NM_000275.3(OCA2):c.2338+1G>T]

NM_000275.3(OCA2):c.2338+1G>T

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.2338+1G>T

HGVS:

NC_000015.10:g.27851381C>A
NG_009846.1:g.252932G>T
NG_009846.2:g.252934G>T
NM_000275.3:c.2338+1G>TMANE SELECT
NM_001300984.2:c.2266+1G>T
NC_000015.9:g.28096527C>A

Links:

dbSNP: rs770635415

NCBI 1000 Genomes Browser:

rs770635415

Molecular consequence:

NM_000275.3:c.2338+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001300984.2:c.2266+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV002226044	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 10, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 29345414, 16199547, 19865097, 21541274, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002226044

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 10, 2023)

germline

clinical testing

PubMed (5)
[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

Molecular characterization of a series of 990 index patients with albinism.

Lasseaux E, Plaisant C, Michaud V, Pennamen P, Trimouille A, Gaston L, Monfermé S, Lacombe D, Rooryck C, Morice-Picard F, Arveiler B.

Pigment Cell Melanoma Res. 2018 Jul;31(4):466-474. doi: 10.1111/pcmr.12688. Epub 2018 Feb 14.

PubMed [citation]

PMID:: 29345414

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002226044.3

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

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1439928). Disruption of this splice site has been observed in individual(s) with oculocutaneous albinism (PMID: 29345414). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs770635415, gnomAD 0.007%). This sequence change affects a donor splice site in intron 22 of the OCA2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in OCA2 are known to be pathogenic (PMID: 19865097, 21541274).

#	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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