NM_000275.3:c.1117-17T>C

Variant names:

• chr15-27989683-A-G
• rs200081580
• NM_000275.3:c.1117-17T>C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BS2_Supporting

The NM_000275.3(OCA2):​c.1117-17T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000992 in 1,613,316 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00074 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (2 hom.)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1 U:2 B:2
• Conservation: PhyloP100: 0.236

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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BS2: High Homozygotes in GnomAdExome4 at 2 AD,AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.1117-17T>C		intron_variant	Intron 10 of 23	ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.1117-17T>C		intron_variant	Intron 10 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.1045-17T>C		intron_variant	Intron 9 of 22	1		ENSP00000261276.8

Frequencies

GnomAD3 genomes AF: 0.000736 AC: 112 AN: 152082 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00110

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000665 AC: 167 AN: 251104 Hom.: 0 AF XY: 0.000626 AC XY: 85 AN XY: 135718

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00106

Gnomad NFE exome AF: 0.00119

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.00102 AC: 1489 AN: 1461116 Hom.: 2 Cov.: 32 AF XY: 0.000989 AC XY: 719 AN XY: 726892

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00101

Gnomad4 NFE exome AF: 0.00124

Gnomad4 OTH exome AF: 0.000729

GnomAD4 genome AF: 0.000736 AC: 112 AN: 152200 Hom.: 0 Cov.: 32 AF XY: 0.000685 AC XY: 51 AN XY: 74420

Gnomad4 AFR AF: 0.000169

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00110

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.000323 Hom.: 0

Bravo AF: 0.000695

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1 Uncertain:2 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Tyrosinase-positive oculocutaneous albinism Pathogenic:1 Uncertain:1

Jun 04, 2023

Molecular Genetics, University Hospital Bordeaux

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing;in vitro

- -

Nov 07, 2021

Genome-Nilou Lab

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Uncertain:1 Benign:1

Apr 24, 2019

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In silico analysis, which includes splice predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Nucleotide substitution has no predicted effect on splicing and is not conserved across species; This variant is associated with the following publications: (PMID: 29345414) -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Likely 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	-0.67
CADD	Benign	12
DANN	Benign	0.64

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

Other links and lift over

dbSNP: rs200081580; hg19: chr15-28234829;