chr15-27845027-C-T

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.2364G>A(p.Ser788Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,612,506 control chromosomes in the GnomAD database, including 46,174 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4160 hom., cov: 32)

Exomes 𝑓: 0.22 ( 42014 hom. )

Consequence

OCA2
NM_000275.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.606

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=-0.56).

BP6

Variant 15-27845027-C-T is Benign according to our data. Variant chr15-27845027-C-T is described in ClinVar as [Benign]. Clinvar id is 255730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.606 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3 link	c.2364G>A	p.Ser788Ser	synonymous_variant	Exon 23 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.2364G>A	p.Ser788Ser	synonymous_variant	Exon 23 of 24	1	NM_000275.3	ENSP00000346659.3		Q04671-1
OCA2	ENST00000353809.9 link	c.2292G>A	p.Ser764Ser	synonymous_variant	Exon 22 of 23	1		ENSP00000261276.8		Q04671-2

Frequencies

GnomAD3 genomes

AF:

0.210

AC:

31785

AN:

151700

Hom.:

4157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.424

Gnomad AMR

AF:

0.331

Gnomad ASJ

AF:

0.313

Gnomad EAS

AF:

0.563

Gnomad SAS

AF:

0.311

Gnomad FIN

AF:

0.255

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.193

Gnomad OTH

AF:

0.212

GnomAD3 exomes

AF:

0.277

AC:

69666

AN:

251336

Hom.:

11865

AF XY:

0.274

AC XY:

37199

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.107

Gnomad AMR exome

AF:

0.449

Gnomad ASJ exome

AF:

0.320

Gnomad EAS exome

AF:

0.564

Gnomad SAS exome

AF:

0.309

Gnomad FIN exome

AF:

0.240

Gnomad NFE exome

AF:

0.198

Gnomad OTH exome

AF:

0.261

GnomAD4 exome

AF:

0.223

AC:

325647

AN:

1460688

Hom.:

42014

Cov.:

AF XY:

0.225

AC XY:

163383

AN XY:

726708

show subpopulations

Gnomad4 AFR exome

AF:

0.101

Gnomad4 AMR exome

AF:

0.435

Gnomad4 ASJ exome

AF:

0.324

Gnomad4 EAS exome

AF:

0.586

Gnomad4 SAS exome

AF:

0.312

Gnomad4 FIN exome

AF:

0.232

Gnomad4 NFE exome

AF:

0.194

Gnomad4 OTH exome

AF:

0.240

GnomAD4 genome

AF:

0.209

AC:

31805

AN:

151818

Hom.:

4160

Cov.:

AF XY:

0.219

AC XY:

16240

AN XY:

74182

show subpopulations

Gnomad4 AFR

AF:

0.111

Gnomad4 AMR

AF:

0.332

Gnomad4 ASJ

AF:

0.313

Gnomad4 EAS

AF:

0.563

Gnomad4 SAS

AF:

0.311

Gnomad4 FIN

AF:

0.255

Gnomad4 NFE

AF:

0.193

Gnomad4 OTH

AF:

0.213

Alfa

AF:

0.203

Hom.:

3922

Bravo

AF:

0.214

Asia WGS

AF:

0.416

AC:

1446

AN:

3478

EpiCase

AF:

0.216

EpiControl

AF:

0.209

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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

- -

Nov 12, 2018

GeneDx

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 specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.11

DANN

Benign

0.54

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

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