NM_000275.3:c.1365-15C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000275.3(OCA2):c.1365-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 1,612,918 control chromosomes in the GnomAD database, including 345,499 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 23976 hom., cov: 32)

Exomes 𝑓: 0.64 ( 321523 hom. )

Consequence

OCA2
NM_000275.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.0380

Publications

21 publications found

Variant links:

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

OCA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 15-27983498-G-A is Benign according to our data. Variant chr15-27983498-G-A is described in ClinVar as Benign. ClinVar VariationId is 255720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3 link	c.1365-15C>T		intron_variant	Intron 13 of 23	ENST00000354638.8	NP_000266.2	Q04671-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8 link	c.1365-15C>T		intron_variant	Intron 13 of 23	1	NM_000275.3	ENSP00000346659.3		Q04671-1
OCA2	ENST00000353809.9 link	c.1293-15C>T		intron_variant	Intron 12 of 22	1		ENSP00000261276.8		Q04671-2

Frequencies

GnomAD3 genomes

AF:

0.506

AC:

76875

AN:

151970

Hom.:

23984

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.738

Gnomad AMR

AF:

0.428

Gnomad ASJ

AF:

0.594

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.346

Gnomad FIN

AF:

0.743

Gnomad MID

AF:

0.636

Gnomad NFE

AF:

0.712

Gnomad OTH

AF:

0.511

GnomAD2 exomes

AF:

0.541

AC:

136088

AN:

251344

AF XY:

0.547

show subpopulations

Gnomad AFR exome

AF:

0.177

Gnomad AMR exome

AF:

0.371

Gnomad ASJ exome

AF:

0.593

Gnomad EAS exome

AF:

0.145

Gnomad FIN exome

AF:

0.742

Gnomad NFE exome

AF:

0.714

Gnomad OTH exome

AF:

0.594

GnomAD4 exome

AF:

0.644

AC:

941109

AN:

1460830

Hom.:

321523

Cov.:

AF XY:

0.638

AC XY:

463606

AN XY:

726796

show subpopulations

African (AFR)

AF:

0.167

AC:

5586

AN:

33458

American (AMR)

AF:

0.381

AC:

17028

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.596

AC:

15564

AN:

26128

East Asian (EAS)

AF:

0.116

AC:

4612

AN:

39698

South Asian (SAS)

AF:

0.365

AC:

31495

AN:

86230

European-Finnish (FIN)

AF:

0.743

AC:

39650

AN:

53398

Middle Eastern (MID)

AF:

0.583

AC:

3362

AN:

5764

European-Non Finnish (NFE)

AF:

0.709

AC:

787827

AN:

1111066

Other (OTH)

AF:

0.596

AC:

35985

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

15692

31384

47076

62768

78460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19190

38380

57570

76760

95950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.505

AC:

76857

AN:

152088

Hom.:

23976

Cov.:

AF XY:

0.500

AC XY:

37181

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.185

AC:

7659

AN:

41470

American (AMR)

AF:

0.428

AC:

6532

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.594

AC:

2063

AN:

3472

East Asian (EAS)

AF:

0.147

AC:

759

AN:

5166

South Asian (SAS)

AF:

0.346

AC:

1665

AN:

4812

European-Finnish (FIN)

AF:

0.743

AC:

7870

AN:

10592

Middle Eastern (MID)

AF:

0.639

AC:

188

AN:

294

European-Non Finnish (NFE)

AF:

0.712

AC:

48374

AN:

67978

Other (OTH)

AF:

0.508

AC:

1074

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1509

3018

4526

6035

7544

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

644

1288

1932

2576

3220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.629

Hom.:

19827

Bravo

AF:

0.472

Asia WGS

AF:

0.296

AC:

1030

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 09, 2017

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Tyrosinase-positive oculocutaneous albinism

Benign:2

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. -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.0

(source)

DANN

Benign

0.50

PhyloP100

0.038

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over