rs1555375711

Variant names:

• chr15-28018396-CCTGCTGTGGCCGCCGCCACCTGGAGCCCAAAGCGTCAGCCTGGGTCAGCTCCACCACGATGTGCTCTTCCCTCCCAGGACGACTCGGCCCACTGGCCACTAGGGCCCCTGCCAGGTCCACCTGCAGCAGCGTGGAGTCCACGTGGCTGCTAAGGTTCACGG-C
• rs1555375711
• NM_000275.3:c.647_807del

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_000275.3(OCA2):​c.647_807del variant causes a exon loss, splice region change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: OCA2 NM_000275.3 exon_loss, splice_region
• Clinical Significance: Pathogenic no assertion criteria provided P:3
• Conservation: PhyloP100: 6.48

Genes affected

OCA2 (HGNC:8101): (OCA2 melanosomal transmembrane protein) This gene encodes the human homolog of the mouse p (pink-eyed dilution) gene. The encoded protein is believed to be an integral membrane protein involved in small molecule transport, specifically tyrosine, which is a precursor to melanin synthesis. It is involved in mammalian pigmentation, where it may control skin color variation and act as a determinant of brown or blue eye color. Mutations in this gene result in type 2 oculocutaneous albinism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 15-28018396-CCTGCTGTGGCCGCCGCCACCTGGAGCCCAAAGCGTCAGCCTGGGTCAGCTCCACCACGATGTGCTCTTCCCTCCCAGGACGACTCGGCCCACTGGCCACTAGGGCCCCTGCCAGGTCCACCTGCAGCAGCGTGGAGTCCACGTGGCTGCTAAGGTTCACGG-C is Pathogenic according to our data. Variant chr15-28018396-CCTGCTGTGGCCGCCGCCACCTGGAGCCCAAAGCGTCAGCCTGGGTCAGCTCCACCACGATGTGCTCTTCCCTCCCAGGACGACTCGGCCCACTGGCCACTAGGGCCCCTGCCAGGTCCACCTGCAGCAGCGTGGAGTCCACGTGGCTGCTAAGGTTCACGG-C is described in ClinVar as [Pathogenic]. Clinvar id is 952.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.647_807del		exon_loss_variant, splice_region_variant	Exon 7 of 24	ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.647_807del		exon_loss_variant, splice_region_variant	Exon 7 of 24	1	NM_000275.3	ENSP00000346659.3

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:3

Revision: no assertion criteria provided

Submissions by phenotype

Tyrosinase-positive oculocutaneous albinism Pathogenic:2

Sep 26, 2019

Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 01, 2007

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Brown oculocutaneous albinism Pathogenic:1

Jan 01, 2007

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1555375711; hg19: chr15-28263542;