VCV000000952.4 - ClinVar

NC_000015.10:g.28018399_28018559del

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(3)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NC_000015.10:g.28018399_28018559del

Variation ID: 952 Accession: VCV000000952.4

Type and length

Deletion, 161 bp

Location

Cytogenetic: 15q13.1 15: 28018397-28018557 (GRCh38) [ NCBI UCSC ] 15: 28263543-28263703 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Apr 27, 2015	Jan 4, 2020	Sep 26, 2019

HGVS

Nucleotide	Protein	Molecular consequence
NC_000015.10:g.28018399_28018559del
NC_000015.9:g.28263545_28263705del
NG_009846.1:g.85756_85916del
NG_009846.2:g.85758_85918del

Protein change

Other names

NM_000275.2:c.647_807del
2.7-KB DEL, EX7DEL

Canonical SPDI

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA026559 OMIM: 611409.0001 dbSNP: rs1555375711 VarSome

Comment on variant

Established a molecular definition at the genomic level from the paper by Gao et al., 2017 (PubMed 28451379).

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
OCA2		-	-	GRCh38 GRCh38 GRCh38 GRCh37	1314	1623

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Tyrosinase-positive oculocutaneous albinism	Pathogenic (2)	no assertion criteria provided	Sep 26, 2019	RCV000001002.14
Brown oculocutaneous albinism	Pathogenic (1)	no assertion criteria provided	Jan 1, 2007	RCV000001003.13

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Jan 01, 2007)	no assertion criteria provided Method: literature only	ALBINISM, OCULOCUTANEOUS, TYPE II Affected status: not provided Allele origin: germline	OMIM Accession: SCV000021152.2 First in ClinVar: Apr 04, 2013 Last updated: Apr 27, 2015	Publications: PubMed (3) PubMed: 7920637‚ 11179026‚ 17767372 Manga, P. Identification and (more...) Manga, P. Identification and molecular characterisation of the genes for brown and rufous oculocutaneous albinism in southern Africa. Ph.D. Thesis: University of the Witwatersrand, Johannesburg 1997. Comment on evidence: In affected members of a consanguineous kindred with oculocutaneous albinism type II (OCA2; 203200), Durham-Pierre et al. (1994) identified a homozygous 2.7-kb deletion encompassing an … (more) In affected members of a consanguineous kindred with oculocutaneous albinism type II (OCA2; 203200), Durham-Pierre et al. (1994) identified a homozygous 2.7-kb deletion encompassing an exon of the P gene. The kindred was of African, Caucasian, and American Indian descent. The same deletion allele was identified in unrelated African Americans, Haitian, and Africans with OCA2, suggesting a founder effect. Brown oculocutaneous albinism (BOCA) is also linked to the P locus, and the occurrence of both OCA2 and BOCA within the same family suggested that these disorders are allelic. Manga (1997) found that a large proportion (9/10) of BOCA subjects were compound heterozygotes with the 2.7-kb deletion of the OCA2 gene on one allele. Manga et al. (2001) demonstrated that 10 persons with brown oculocutaneous albinism in southern Africa were heterozygous for the 2.7-kb deletion. They did not succeed in defining the second mutation but presumed that it was a milder mutation, possibly in the promoter region (downregulating expression) or in other regions of the P gene they did not screen. By analyzing a 5-SNP haplotype of the OCA2 gene in 53 unrelated Cameroonian OCA2 patients homozygous for the 2.7-kb deletion and 48 ethnically matched controls, Aquaron et al. (2007) estimated that the mutation originated 4,100 to 5,645 years ago. (less)
Pathogenic (Jan 01, 2007)	no assertion criteria provided Method: literature only	BROWN OCULOCUTANEOUS ALBINISM Affected status: not provided Allele origin: germline	OMIM Accession: SCV000021153.2 First in ClinVar: Apr 04, 2013 Last updated: Apr 27, 2015	Publications: PubMed (3) PubMed: 7920637‚ 11179026‚ 17767372 Manga, P. Identification and (more...) Manga, P. Identification and molecular characterisation of the genes for brown and rufous oculocutaneous albinism in southern Africa. Ph.D. Thesis: University of the Witwatersrand, Johannesburg 1997. Comment on evidence: In affected members of a consanguineous kindred with oculocutaneous albinism type II (OCA2; 203200), Durham-Pierre et al. (1994) identified a homozygous 2.7-kb deletion encompassing an … (more) In affected members of a consanguineous kindred with oculocutaneous albinism type II (OCA2; 203200), Durham-Pierre et al. (1994) identified a homozygous 2.7-kb deletion encompassing an exon of the P gene. The kindred was of African, Caucasian, and American Indian descent. The same deletion allele was identified in unrelated African Americans, Haitian, and Africans with OCA2, suggesting a founder effect. Brown oculocutaneous albinism (BOCA) is also linked to the P locus, and the occurrence of both OCA2 and BOCA within the same family suggested that these disorders are allelic. Manga (1997) found that a large proportion (9/10) of BOCA subjects were compound heterozygotes with the 2.7-kb deletion of the OCA2 gene on one allele. Manga et al. (2001) demonstrated that 10 persons with brown oculocutaneous albinism in southern Africa were heterozygous for the 2.7-kb deletion. They did not succeed in defining the second mutation but presumed that it was a milder mutation, possibly in the promoter region (downregulating expression) or in other regions of the P gene they did not screen. By analyzing a 5-SNP haplotype of the OCA2 gene in 53 unrelated Cameroonian OCA2 patients homozygous for the 2.7-kb deletion and 48 ethnically matched controls, Aquaron et al. (2007) estimated that the mutation originated 4,100 to 5,645 years ago. (less)
Pathogenic (Sep 26, 2019)	no assertion criteria provided Method: clinical testing	Tyrosinase-positive oculocutaneous albinism Affected status: yes Allele origin: germline	Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City Accession: SCV001133108.1 First in ClinVar: Jan 04, 2020 Last updated: Jan 04, 2020

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Oculocutaneous albinism type 2 (OCA2) with homozygous 2.7-kb deletion of the P gene and sickle cell disease in a Cameroonian family. Identification of a common TAG haplotype in the mutated P gene.	Aquaron R	Journal of human genetics	2007	PMID: 17767372
In Southern Africa, brown oculocutaneous albinism (BOCA) maps to the OCA2 locus on chromosome 15q: P-gene mutations identified.	Manga P	American journal of human genetics	2001	PMID: 11179026
African origin of an intragenic deletion of the human P gene in tyrosinase positive oculocutaneous albinism.	Durham-Pierre D	Nature genetics	1994	PMID: 7920637
Manga, P. Identification and molecular characterisation of the genes for brown and rufous oculocutaneous albinism in southern Africa. Ph.D. Thesis: University of the Witwatersrand, Johannesburg 1997.	-	-	-	-

Text-mined citations for rs1555375711 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 25, 2024

ClinVar Genomic variation as it relates to human health

NC_000015.10:g.28018399_28018559del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1555375711 ...