chr15-27986647-T-C

Variant names:

• chr15-27986647-T-C
• rs10852218
• NM_000275.3:c.1183-4A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000275.3(OCA2):​c.1183-4A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 1,552,170 control chromosomes in the GnomAD database, including 500,432 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (41604 hom., cov: 32)
  • Exomes 𝑓: 0.80 (458828 hom.)
• Consequence: OCA2 NM_000275.3 splice_region, intron
• Scores: Splicing: ADA: 0.00003896
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.153
• Publications: 22 publications found

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]

OCA2 Gene-Disease associations (from GenCC):

• oculocutaneous albinism type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P, ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 15-27986647-T-C is Benign according to our data. Variant chr15-27986647-T-C is described in ClinVar as Benign. ClinVar VariationId is 193986.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.1183-4A>G		splice_region_variant, intron_variant	Intron 11 of 23	ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.1183-4A>G		splice_region_variant, intron_variant	Intron 11 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.1111-4A>G		splice_region_variant, intron_variant	Intron 10 of 22	1		ENSP00000261276.8

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109567 AN: 152034 Hom.: 41603 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.872

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.735

GnomAD2 exomes AF: 0.782 AC: 196675 AN: 251390 AF XY: 0.780

Gnomad AFR exome AF: 0.466

Gnomad AMR exome AF: 0.726

Gnomad ASJ exome AF: 0.817

Gnomad EAS exome AF: 0.998

Gnomad FIN exome AF: 0.872

Gnomad NFE exome AF: 0.836

Gnomad OTH exome AF: 0.796

GnomAD4 exome AF: 0.804 AC: 1126263 AN: 1400018 Hom.: 458828 Cov.: 27 AF XY: 0.800 AC XY: 560357 AN XY: 700506

African (AFR) AF: 0.453 AC: 14781 AN: 32624

American (AMR) AF: 0.724 AC: 32324 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.819 AC: 21130 AN: 25800

East Asian (EAS) AF: 0.999 AC: 39300 AN: 39350

South Asian (SAS) AF: 0.619 AC: 52678 AN: 85164

European-Finnish (FIN) AF: 0.870 AC: 46484 AN: 53404

Middle Eastern (MID) AF: 0.781 AC: 4422 AN: 5660

European-Non Finnish (NFE) AF: 0.824 AC: 869449 AN: 1055092

Other (OTH) AF: 0.784 AC: 45695 AN: 58282

GnomAD4 genome AF: 0.720 AC: 109600 AN: 152152 Hom.: 41604 Cov.: 32 AF XY: 0.721 AC XY: 53665 AN XY: 74398

African (AFR) AF: 0.472 AC: 19576 AN: 41484

American (AMR) AF: 0.700 AC: 10699 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 2823 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5178 AN: 5188

South Asian (SAS) AF: 0.616 AC: 2971 AN: 4820

European-Finnish (FIN) AF: 0.872 AC: 9238 AN: 10598

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.832 AC: 56543 AN: 67998

Other (OTH) AF: 0.732 AC: 1544 AN: 2108

Alfa AF: 0.781 Hom.: 24823

Bravo AF: 0.704

Asia WGS AF: 0.789 AC: 2742 AN: 3478

EpiCase AF: 0.820

EpiControl AF: 0.816

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Jun 20, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 07, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Tyrosinase-positive oculocutaneous albinism Benign:2

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.22
DANN	Benign	0.67
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000039
dbscSNV1_RF	Benign	0.010
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

Other links and lift over

dbSNP: rs10852218; hg19: chr15-28231793;