15-27851392-A-G

Variant names:

• chr15-27851392-A-G
• rs1800419
• NM_000275.3:c.2328T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000275.3(OCA2):​c.2328T>C​(p.Ala776Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 1,612,484 control chromosomes in the GnomAD database, including 152,875 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17884 hom., cov: 32)
  • Exomes 𝑓: 0.43 (134991 hom.)
• Consequence: OCA2 NM_000275.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 1.39
• Publications: 27 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 15-27851392-A-G is Benign according to our data. Variant chr15-27851392-A-G is described in ClinVar as Benign. ClinVar VariationId is 195643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.39 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000275.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	NM_000275.3	MANE Select	c.2328T>C	p.Ala776Ala	synonymous	Exon 22 of 24	NP_000266.2
	OCA2	NM_001300984.2		c.2256T>C	p.Ala752Ala	synonymous	Exon 21 of 23	NP_001287913.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	ENST00000354638.8	TSL:1 MANE Select	c.2328T>C	p.Ala776Ala	synonymous	Exon 22 of 24	ENSP00000346659.3
	OCA2	ENST00000353809.9	TSL:1	c.2256T>C	p.Ala752Ala	synonymous	Exon 21 of 23	ENSP00000261276.8

Frequencies

GnomAD3 genomes AF: 0.474 AC: 72097 AN: 151952 Hom.: 17866 Cov.: 32

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.533

GnomAD2 exomes AF: 0.435 AC: 107811 AN: 248098 AF XY: 0.439

Gnomad AFR exome AF: 0.623

Gnomad AMR exome AF: 0.365

Gnomad ASJ exome AF: 0.481

Gnomad EAS exome AF: 0.438

Gnomad FIN exome AF: 0.335

Gnomad NFE exome AF: 0.416

Gnomad OTH exome AF: 0.447

GnomAD4 exome AF: 0.425 AC: 621378 AN: 1460416 Hom.: 134991 Cov.: 39 AF XY: 0.429 AC XY: 311663 AN XY: 726484

African (AFR) AF: 0.629 AC: 21040 AN: 33464

American (AMR) AF: 0.373 AC: 16633 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 12607 AN: 26108

East Asian (EAS) AF: 0.417 AC: 16554 AN: 39660

South Asian (SAS) AF: 0.526 AC: 45281 AN: 86116

European-Finnish (FIN) AF: 0.334 AC: 17841 AN: 53360

Middle Eastern (MID) AF: 0.531 AC: 3049 AN: 5746

European-Non Finnish (NFE) AF: 0.415 AC: 461257 AN: 1110974

Other (OTH) AF: 0.449 AC: 27116 AN: 60342

GnomAD4 genome AF: 0.474 AC: 72148 AN: 152068 Hom.: 17884 Cov.: 32 AF XY: 0.471 AC XY: 35047 AN XY: 74332

African (AFR) AF: 0.617 AC: 25619 AN: 41498

American (AMR) AF: 0.427 AC: 6525 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1694 AN: 3468

East Asian (EAS) AF: 0.440 AC: 2260 AN: 5136

South Asian (SAS) AF: 0.537 AC: 2585 AN: 4818

European-Finnish (FIN) AF: 0.323 AC: 3415 AN: 10582

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.419 AC: 28498 AN: 67968

Other (OTH) AF: 0.536 AC: 1132 AN: 2112

Alfa AF: 0.449 Hom.: 11341

Bravo AF: 0.486

Asia WGS AF: 0.491 AC: 1708 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Jan 21, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Tyrosinase-positive oculocutaneous albinism Benign:2

Jan 12, 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.

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Tyrosinase-positive oculocutaneous albinism;C1856895:SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES Benign:1

Mar 17, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	8.2
DANN	Benign	0.55
PhyloP100		1.4
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1800419; hg19: chr15-28096538; COSMIC: COSV62337410;