15-27832014-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000275.3(OCA2):c.2432+12945A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 150,914 control chromosomes in the GnomAD database, including 44,007 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 0.75 (44007 hom., cov: 27)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.85

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]

ACMG classification

Verdict is Benign. Variant got -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 = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OCA2	NM_000275.3	c.2432+12945A>G		intron_variant		ENST00000354638.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCA2	ENST00000354638.8	c.2432+12945A>G		intron_variant		1	NM_000275.3	P1
OCA2	ENST00000353809.9	c.2360+12945A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.751 AC: 113280 AN: 150796 Hom.: 43951 Cov.: 27

Gnomad AFR AF: 0.899

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.886

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.846

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.815

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

GnomAD4 genome AF: 0.751 AC: 113396 AN: 150914 Hom.: 44007 Cov.: 27 AF XY: 0.754 AC XY: 55523 AN XY: 73608

Gnomad4 AFR AF: 0.899

Gnomad4 AMR AF: 0.813

Gnomad4 ASJ AF: 0.783

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.886

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.643

Gnomad4 OTH AF: 0.817

Alfa AF: 0.445 Hom.: 758

Bravo AF: 0.776

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.2
Dann	Benign	0.28

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

Publications

LitVar

Other links and lift over

dbSNP: rs4778190; hg19: chr15-28077160;