chr15-27986647-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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:7
• Conservation: PhyloP100: -0.153

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 193986.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-27986647-T-C is described in Lovd as [Benign].
• 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

GnomAD3 exomes AF: 0.782 AC: 196675 AN: 251390 Hom.: 79212 AF XY: 0.780 AC XY: 105988 AN XY: 135866

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 SAS exome AF: 0.608

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

Gnomad4 AFR exome AF: 0.453

Gnomad4 AMR exome AF: 0.724

Gnomad4 ASJ exome AF: 0.819

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.619

Gnomad4 FIN exome AF: 0.870

Gnomad4 NFE exome AF: 0.824

Gnomad4 OTH exome AF: 0.784

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

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.700

Gnomad4 ASJ AF: 0.813

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.616

Gnomad4 FIN AF: 0.872

Gnomad4 NFE AF: 0.832

Gnomad4 OTH AF: 0.732

Alfa AF: 0.782 Hom.: 24017

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:7

Revision: criteria provided, multiple submitters, no conflicts

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

- -

not specified Benign:2

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

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.22
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs10852218; hg19: chr15-28231793;