NM_000275.3:c.1065G>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000275.3(OCA2):c.1065G>A(p.Ala355Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 1,613,344 control chromosomes in the GnomAD database, including 438,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 31157 hom., cov: 33)

Exomes 𝑓: 0.73 ( 407137 hom. )

Consequence

OCA2
NM_000275.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.25

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 15-27990627-C-T is Benign according to our data. Variant chr15-27990627-C-T is described in ClinVar as [Benign]. Clinvar id is 255716.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-27990627-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.25 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3 link	c.1065G>A	p.Ala355Ala	synonymous_variant	Exon 10 of 24	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.1065G>A	p.Ala355Ala	synonymous_variant	Exon 10 of 24	1	NM_000275.3	ENSP00000346659.3		Q04671-1
OCA2	ENST00000353809.9 link	c.1045-961G>A		intron_variant	Intron 9 of 22	1		ENSP00000261276.8		Q04671-2

Frequencies

GnomAD3 genomes

AF:

0.586

AC:

89073

AN:

151998

Hom.:

31163

Cov.:

show subpopulations

Gnomad AFR

AF:

0.215

Gnomad AMI

AF:

0.770

Gnomad AMR

AF:

0.571

Gnomad ASJ

AF:

0.715

Gnomad EAS

AF:

0.400

Gnomad SAS

AF:

0.363

Gnomad FIN

AF:

0.839

Gnomad MID

AF:

0.753

Gnomad NFE

AF:

0.794

Gnomad OTH

AF:

0.629

GnomAD3 exomes

AF:

0.639

AC:

160311

AN:

251022

Hom.:

56793

AF XY:

0.640

AC XY:

86886

AN XY:

135692

show subpopulations

Gnomad AFR exome

AF:

0.203

Gnomad AMR exome

AF:

0.536

Gnomad ASJ exome

AF:

0.706

Gnomad EAS exome

AF:

0.382

Gnomad SAS exome

AF:

0.379

Gnomad FIN exome

AF:

0.829

Gnomad NFE exome

AF:

0.798

Gnomad OTH exome

AF:

0.701

GnomAD4 exome

AF:

0.731

AC:

1068472

AN:

1461228

Hom.:

407137

Cov.:

AF XY:

0.723

AC XY:

525916

AN XY:

726944

show subpopulations

Gnomad4 AFR exome

AF:

0.191

Gnomad4 AMR exome

AF:

0.542

Gnomad4 ASJ exome

AF:

0.706

Gnomad4 EAS exome

AF:

0.403

Gnomad4 SAS exome

AF:

0.392

Gnomad4 FIN exome

AF:

0.830

Gnomad4 NFE exome

AF:

0.791

Gnomad4 OTH exome

AF:

0.692

GnomAD4 genome

AF:

0.586

AC:

89067

AN:

152116

Hom.:

31157

Cov.:

AF XY:

0.583

AC XY:

43375

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.215

Gnomad4 AMR

AF:

0.570

Gnomad4 ASJ

AF:

0.715

Gnomad4 EAS

AF:

0.399

Gnomad4 SAS

AF:

0.363

Gnomad4 FIN

AF:

0.839

Gnomad4 NFE

AF:

0.794

Gnomad4 OTH

AF:

0.624

Alfa

AF:

0.725

Hom.:

52744

Bravo

AF:

0.557

Asia WGS

AF:

0.432

AC:

1506

AN:

3478

EpiCase

AF:

0.783

EpiControl

AF:

0.780

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 17, 2015

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

-0.52

CADD

Benign

0.35

DANN

Benign

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over