rs1800405

Positions:

• chr15-27990579-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000275.3(OCA2):​c.1113C>T​(p.Gly371=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,613,562 control chromosomes in the GnomAD database, including 479 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (72 hom., cov: 32)
  • Exomes 𝑓: 0.014 (407 hom.)
• Consequence: OCA2 NM_000275.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.64

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-27990579-G-A is Benign according to our data. Variant chr15-27990579-G-A is described in ClinVar as [Benign]. Clinvar id is 193573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.64 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OCA2	NM_000275.3	c.1113C>T	p.Gly371=	synonymous_variant	10/24	ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.1113C>T	p.Gly371=	synonymous_variant	10/24	1	NM_000275.3	ENSP00000346659	P1
OCA2	ENST00000353809.9	c.1045-913C>T		intron_variant		1		ENSP00000261276

Frequencies

GnomAD3 genomes AF: 0.0165 AC: 2517 AN: 152126 Hom.: 71 Cov.: 32

Gnomad AFR AF: 0.00357

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0842

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0111

Gnomad OTH AF: 0.0220

GnomAD3 exomes AF: 0.0243 AC: 6102 AN: 251046 Hom.: 244 AF XY: 0.0218 AC XY: 2958 AN XY: 135686

Gnomad AFR exome AF: 0.00234

Gnomad AMR exome AF: 0.105

Gnomad ASJ exome AF: 0.00676

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.0245

Gnomad FIN exome AF: 0.0125

Gnomad NFE exome AF: 0.0107

Gnomad OTH exome AF: 0.0204

GnomAD4 exome AF: 0.0138 AC: 20138 AN: 1461318 Hom.: 407 Cov.: 30 AF XY: 0.0138 AC XY: 10024 AN XY: 726988

Gnomad4 AFR exome AF: 0.00218

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.00742

Gnomad4 EAS exome AF: 0.000202

Gnomad4 SAS exome AF: 0.0252

Gnomad4 FIN exome AF: 0.0125

Gnomad4 NFE exome AF: 0.0104

Gnomad4 OTH exome AF: 0.0136

GnomAD4 genome AF: 0.0166 AC: 2525 AN: 152244 Hom.: 72 Cov.: 32 AF XY: 0.0181 AC XY: 1349 AN XY: 74440

Gnomad4 AFR AF: 0.00356

Gnomad4 AMR AF: 0.0847

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0226

Gnomad4 FIN AF: 0.0136

Gnomad4 NFE AF: 0.0111

Gnomad4 OTH AF: 0.0217

Alfa AF: 0.0107 Hom.: 8

Bravo AF: 0.0211

Asia WGS AF: 0.0120 AC: 43 AN: 3478

EpiCase AF: 0.00987

EpiControl AF: 0.0108

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 27884173, 21541274) -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 29, 2014	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Tyrosinase-positive oculocutaneous albinism Benign:2

Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.45
DANN	Benign	0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1800405; hg19: chr15-28235725; COSMIC: COSV62347626;