15-27776815-T-G

Position:

• chr15-27776815-T-G

Variant summary

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

The NM_000275.3(OCA2):​c.2433-21343A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,238 control chromosomes in the GnomAD database, including 2,302 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 0.14 (2302 hom., cov: 31)
  • Exomes 𝑓: 0.032 (0 hom.)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OCA2	NM_000275.3	c.2433-21343A>C		intron_variant		ENST00000354638.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCA2	ENST00000354638.8	c.2433-21343A>C		intron_variant		1	NM_000275.3	P1
OCA2	ENST00000353809.9	c.2361-21343A>C		intron_variant		1
	ENST00000419100.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20658 AN: 151966 Hom.: 2301 Cov.: 31

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0712

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0598

Gnomad OTH AF: 0.122

GnomAD4 exome AF: 0.0325 AC: 5 AN: 154 Hom.: 0 Cov.: 0 AF XY: 0.0179 AC XY: 2 AN XY: 112

Gnomad4 AFR exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0403

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.136 AC: 20674 AN: 152084 Hom.: 2302 Cov.: 31 AF XY: 0.143 AC XY: 10611 AN XY: 74348

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.0712

Gnomad4 EAS AF: 0.586

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.0598

Gnomad4 OTH AF: 0.123

Alfa AF: 0.0372 Hom.: 43

Bravo AF: 0.143

Asia WGS AF: 0.309 AC: 1074 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.3
DANN	Benign	0.74

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: rs2279727; hg19: chr15-28021961;