15-27789763-C-T

Variant names:

• chr15-27789763-C-T
• rs7171246
• NM_000275.3:c.2433-34291G>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.2433-34291G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 151,970 control chromosomes in the GnomAD database, including 6,901 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 0.28 (6901 hom., cov: 33)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.429
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.2433-34291G>A		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.2433-34291G>A		intron_variant	Intron 23 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.2361-34291G>A		intron_variant	Intron 22 of 22	1		ENSP00000261276.8

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42096 AN: 151852 Hom.: 6898 Cov.: 33

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.277 AC: 42118 AN: 151970 Hom.: 6901 Cov.: 33 AF XY: 0.271 AC XY: 20094 AN XY: 74264

African (AFR) AF: 0.176 AC: 7299 AN: 41440

American (AMR) AF: 0.208 AC: 3174 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 873 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5180

South Asian (SAS) AF: 0.108 AC: 520 AN: 4822

European-Finnish (FIN) AF: 0.419 AC: 4401 AN: 10500

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.369 AC: 25099 AN: 67966

Other (OTH) AF: 0.223 AC: 470 AN: 2112

Alfa AF: 0.333 Hom.: 1192

Bravo AF: 0.260

Asia WGS AF: 0.0640 AC: 221 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.5
DANN	Benign	0.60
PhyloP100		-0.43
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: rs7171246; hg19: chr15-28034909; COSMIC: COSV62340626;