rs1375166

Variant names:

• chr15-27888228-C-T
• rs1375166
• NM_000275.3:c.2080-16306G>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.2080-16306G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,158 control chromosomes in the GnomAD database, including 3,926 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 0.19 (3926 hom., cov: 32)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.210
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.2080-16306G>A		intron_variant	Intron 19 of 23	ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.2080-16306G>A		intron_variant	Intron 19 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.2008-16306G>A		intron_variant	Intron 18 of 22	1		ENSP00000261276.8

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28834 AN: 152040 Hom.: 3923 Cov.: 32

Gnomad AFR AF: 0.0421

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.190 AC: 28840 AN: 152158 Hom.: 3926 Cov.: 32 AF XY: 0.200 AC XY: 14842 AN XY: 74376

African (AFR) AF: 0.0420 AC: 1745 AN: 41548

American (AMR) AF: 0.327 AC: 4998 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1112 AN: 3470

East Asian (EAS) AF: 0.564 AC: 2907 AN: 5152

South Asian (SAS) AF: 0.290 AC: 1401 AN: 4828

European-Finnish (FIN) AF: 0.255 AC: 2704 AN: 10594

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13101 AN: 67972

Other (OTH) AF: 0.199 AC: 419 AN: 2108

Alfa AF: 0.199 Hom.: 1678

Bravo AF: 0.192

Asia WGS AF: 0.401 AC: 1394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.2
DANN	Benign	0.38
PhyloP100		0.21
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: rs1375166; hg19: chr15-28133374;