rs7170989

chr15-27955262-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000275.3(OCA2):c.1785-47A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.697 in 1,386,276 control chromosomes in the GnomAD database, including 357,104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (30680 hom., cov: 34)
  • Exomes 𝑓: 0.71 (326424 hom.)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.147

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 15-27955262-T-C is Benign according to our data. Variant chr15-27955262-T-C is described in ClinVar as [Benign]. Clinvar id is 1252195.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OCA2	NM_000275.3	c.1785-47A>G		intron_variant		ENST00000354638.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCA2	ENST00000354638.8	c.1785-47A>G		intron_variant		1	NM_000275.3	P1
OCA2	ENST00000353809.9	c.1713-47A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91540 AN: 152086 Hom.: 30686 Cov.: 34

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.868

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.606

GnomAD3 exomes AF: 0.613 AC: 153774 AN: 250994 Hom.: 53081 AF XY: 0.620 AC XY: 84222 AN XY: 135734

Gnomad AFR exome AF: 0.366

Gnomad AMR exome AF: 0.412

Gnomad ASJ exome AF: 0.741

Gnomad EAS exome AF: 0.141

Gnomad SAS exome AF: 0.478

Gnomad FIN exome AF: 0.761

Gnomad NFE exome AF: 0.779

Gnomad OTH exome AF: 0.668

GnomAD4 exome AF: 0.709 AC: 874359 AN: 1234072 Hom.: 326424 Cov.: 17 AF XY: 0.704 AC XY: 440477 AN XY: 626018

Gnomad4 AFR exome AF: 0.352

Gnomad4 AMR exome AF: 0.425

Gnomad4 ASJ exome AF: 0.743

Gnomad4 EAS exome AF: 0.108

Gnomad4 SAS exome AF: 0.490

Gnomad4 FIN exome AF: 0.764

Gnomad4 NFE exome AF: 0.777

Gnomad4 OTH exome AF: 0.673

GnomAD4 genome AF: 0.602 AC: 91563 AN: 152204 Hom.: 30680 Cov.: 34 AF XY: 0.596 AC XY: 44339 AN XY: 74418

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.730

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.753

Gnomad4 NFE AF: 0.775

Gnomad4 OTH AF: 0.602

Alfa AF: 0.669 Hom.: 10185

Bravo AF: 0.574

Asia WGS AF: 0.349 AC: 1216 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Tyrosinase-positive oculocutaneous albinism Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	2.5
Dann	Benign	0.33

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: rs7170989; hg19: chr15-28200408; COSMIC: COSV62341571;