rs1498509

Variant names:

• chr15-27784854-G-A
• rs1498509
• NM_000275.3:c.2433-29382C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-27784854-G-A
• chr15-27784854-G-C
• chr15-27784854-G-T

Variant summary

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

The NM_000275.3(OCA2):​c.2433-29382C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 151,724 control chromosomes in the GnomAD database, including 25,487 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 0.56 (25487 hom., cov: 31)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195
• Publications: 3 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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P, ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.2433-29382C>T		intron_variant	Intron 23 of 23	ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.2433-29382C>T		intron_variant	Intron 23 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.2361-29382C>T		intron_variant	Intron 22 of 22	1		ENSP00000261276.8

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84582 AN: 151604 Hom.: 25436 Cov.: 31

Gnomad AFR AF: 0.771

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.558 AC: 84692 AN: 151724 Hom.: 25487 Cov.: 31 AF XY: 0.554 AC XY: 41079 AN XY: 74100

African (AFR) AF: 0.772 AC: 31909 AN: 41352

American (AMR) AF: 0.399 AC: 6087 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1199 AN: 3466

East Asian (EAS) AF: 0.585 AC: 3012 AN: 5146

South Asian (SAS) AF: 0.294 AC: 1413 AN: 4814

European-Finnish (FIN) AF: 0.640 AC: 6707 AN: 10474

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 32989 AN: 67904

Other (OTH) AF: 0.466 AC: 980 AN: 2102

Alfa AF: 0.531 Hom.: 4226

Bravo AF: 0.555

Asia WGS AF: 0.430 AC: 1496 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.52
DANN	Benign	0.20
PhyloP100		-0.20
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: rs1498509; hg19: chr15-28030000;