rs977588

Positions:

• chr15-27934160-C-A
• chr15-27934160-C-G

Variant summary

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

The NM_000275.3(OCA2):​c.1952-7906G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 150,246 control chromosomes in the GnomAD database, including 22,068 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 0.53 (22068 hom., cov: 31)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213

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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OCA2	NM_000275.3	c.1952-7906G>T		intron_variant		ENST00000354638.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCA2	ENST00000354638.8	c.1952-7906G>T		intron_variant		1	NM_000275.3	P1
OCA2	ENST00000353809.9	c.1880-7906G>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80016 AN: 150138 Hom.: 22062 Cov.: 31

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.523

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.533 AC: 80057 AN: 150246 Hom.: 22068 Cov.: 31 AF XY: 0.521 AC XY: 38201 AN XY: 73288

Gnomad4 AFR AF: 0.530

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.555

Gnomad4 NFE AF: 0.597

Gnomad4 OTH AF: 0.522

Alfa AF: 0.562 Hom.: 30666

Bravo AF: 0.525

Asia WGS AF: 0.247 AC: 863 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	0.72
DANN	Benign	0.42

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: rs977588; hg19: chr15-28179306;