NM_000275.3(OCA2):c.1503+5G>A AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 2, 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:: RCV000302408.9

Allele description

NM_000275.3(OCA2):c.1503+5G>A

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.1503+5G>A

HGVS:

NC_000015.10:g.27983340C>T
NG_009846.1:g.120973G>A
NM_000275.3:c.1503+5G>AMANE SELECT
NM_001300984.2:c.1431+5G>A
NC_000015.9:g.28228486C>T
NM_000275.2:c.1503+5G>A

Links:

dbSNP: rs368124046

NCBI 1000 Genomes Browser:

rs368124046

Molecular consequence:

NM_000275.3:c.1503+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001300984.2:c.1431+5G>A - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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zinc finger protein 382 isoform 1 [Homo sapiens]
zinc finger protein 382 isoform 1 [Homo sapiens]
gi|2167384503|ref|NP_001385420.1|

Protein
chromodomain-helicase-DNA-binding protein 7 isoform X1 [Homo sapiens]
chromodomain-helicase-DNA-binding protein 7 isoform X1 [Homo sapiens]
gi|1034660843|ref|XP_016869101.1|

Protein
chromodomain-helicase-DNA-binding protein 7 isoform X4 [Homo sapiens]
chromodomain-helicase-DNA-binding protein 7 isoform X4 [Homo sapiens]
gi|2217372458|ref|XP_047277901.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000329444	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jul 13, 2023)	germline	clinical testing	Citation Link,
SCV002235033	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 2, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 29345414, 17576681, 9536098, 24361966, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000329444

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jul 13, 2023)

germline

clinical testing

Citation Link,

SCV002235033

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 2, 2024)

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
not provided	germline	yes	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

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

See all PubMed Citations (5)

Details of each submission

From GeneDx, SCV000329444.9

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

Description

Intronic +5 splice site variant in a gene for which loss of function is a known mechanism of disease, and splice predictors support a deleterious effect; Published functional studies demonstrate the use of a cryptic splice donor site within intron 14, with sequencing of aberrant transcript demonstrating it results in a frameshift, starting with codon Glycine 502, changing this amino acid to a Valine residue, and creating a premature Stop codon at position 84 of the new reading frame, denoted p.Gly502ValfsX84 (Rimoldi et al., 2014).; This variant is associated with the following publications: (PMID: 15712365, 10649493, 24361966, 31077556)

#	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 Invitae, SCV002235033.3

#	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 falls in intron 14 of the OCA2 gene. It does not directly change the encoded amino acid sequence of the OCA2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs368124046, gnomAD 0.01%). This variant has been observed in individuals with oculocutaneous albinism (PMID: 24361966, 29345414; Invitae). ClinVar contains an entry for this variant (Variation ID: 211768). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 24361966). 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: Jun 17, 2024

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