15-27908182-T-C

Position:

• chr15-27908182-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.2079+17945A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 151,894 control chromosomes in the GnomAD database, including 31,111 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 0.63 (31111 hom., cov: 32)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OCA2	NM_000275.3	c.2079+17945A>G		intron_variant		ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.2079+17945A>G		intron_variant		1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.2007+17945A>G		intron_variant		1		ENSP00000261276.8

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96181 AN: 151776 Hom.: 31088 Cov.: 32

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.964

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.796

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.703

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

GnomAD4 genome AF: 0.634 AC: 96246 AN: 151894 Hom.: 31111 Cov.: 32 AF XY: 0.638 AC XY: 47397 AN XY: 74262

Gnomad4 AFR AF: 0.619

Gnomad4 AMR AF: 0.738

Gnomad4 ASJ AF: 0.783

Gnomad4 EAS AF: 0.964

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.596

Gnomad4 OTH AF: 0.706

Alfa AF: 0.447 Hom.: 1073

Bravo AF: 0.652

Asia WGS AF: 0.736 AC: 2545 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.1
DANN	Benign	0.47

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: rs2703922; hg19: chr15-28153328;