rs12914687

Variant names:

• chr15-27981395-C-T
• rs12914687
• NM_000275.3:c.1503+1950G>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.1503+1950G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 152,114 control chromosomes in the GnomAD database, including 24,260 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 0.51 (24260 hom., cov: 33)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.562
• 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 (NFE) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.1503+1950G>A		intron_variant	Intron 14 of 23	ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.1503+1950G>A		intron_variant	Intron 14 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.1431+1950G>A		intron_variant	Intron 13 of 22	1		ENSP00000261276.8

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77442 AN: 151996 Hom.: 24268 Cov.: 33

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.739

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.516

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

GnomAD4 genome AF: 0.509 AC: 77429 AN: 152114 Hom.: 24260 Cov.: 33 AF XY: 0.504 AC XY: 37487 AN XY: 74354

African (AFR) AF: 0.188 AC: 7797 AN: 41494

American (AMR) AF: 0.432 AC: 6597 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2081 AN: 3468

East Asian (EAS) AF: 0.148 AC: 765 AN: 5176

South Asian (SAS) AF: 0.368 AC: 1773 AN: 4824

European-Finnish (FIN) AF: 0.744 AC: 7870 AN: 10574

Middle Eastern (MID) AF: 0.637 AC: 186 AN: 292

European-Non Finnish (NFE) AF: 0.715 AC: 48604 AN: 67988

Other (OTH) AF: 0.513 AC: 1082 AN: 2110

Alfa AF: 0.595 Hom.: 3996

Bravo AF: 0.475

Asia WGS AF: 0.305 AC: 1061 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	0.21
DANN	Benign	0.60
PhyloP100		-0.56
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: rs12914687; hg19: chr15-28226541;