15-27761160-C-T

Variant names:

• chr15-27761160-C-T
• rs989869
• NM_000275.3:c.2433-5688G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000275.3(OCA2):​c.2433-5688G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 151,476 control chromosomes in the GnomAD database, including 31,074 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.64 (31074 hom., cov: 29)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 5 publications found

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]

OCA2 Gene-Disease associations (from GenCC):

• oculocutaneous albinism type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000275.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	NM_000275.3	MANE Select	c.2433-5688G>A		intron	N/A	NP_000266.2	Q04671-1
	OCA2	NM_001300984.2		c.2361-5688G>A		intron	N/A	NP_001287913.1	Q04671-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	ENST00000354638.8	TSL:1 MANE Select	c.2433-5688G>A		intron	N/A	ENSP00000346659.3	Q04671-1
	OCA2	ENST00000353809.9	TSL:1	c.2361-5688G>A		intron	N/A	ENSP00000261276.8	Q04671-2
	OCA2	ENST00000910120.1		c.2679-5688G>A		intron	N/A	ENSP00000580179.1

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96543 AN: 151358 Hom.: 31040 Cov.: 29

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.574

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

GnomAD4 genome AF: 0.638 AC: 96631 AN: 151476 Hom.: 31074 Cov.: 29 AF XY: 0.639 AC XY: 47305 AN XY: 74004

African (AFR) AF: 0.686 AC: 28353 AN: 41320

American (AMR) AF: 0.607 AC: 9253 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1877 AN: 3464

East Asian (EAS) AF: 0.715 AC: 3677 AN: 5142

South Asian (SAS) AF: 0.654 AC: 3143 AN: 4806

European-Finnish (FIN) AF: 0.679 AC: 7091 AN: 10440

Middle Eastern (MID) AF: 0.503 AC: 147 AN: 292

European-Non Finnish (NFE) AF: 0.613 AC: 41509 AN: 67762

Other (OTH) AF: 0.577 AC: 1213 AN: 2102

Alfa AF: 0.621 Hom.: 16266

Bravo AF: 0.634

Asia WGS AF: 0.711 AC: 2462 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.24
DANN	Benign	0.081
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs989869; hg19: chr15-28006306;