rs1800411

chr15-27966775-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.1551C>T(p.Cys517=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 1,612,640 control chromosomes in the GnomAD database, including 352,262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (25293 hom., cov: 32)
  • Exomes 𝑓: 0.65 (326969 hom.)
• Consequence: OCA2 NM_000275.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 2.05

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=-0.47).
• BP6: Variant 15-27966775-G-A is Benign according to our data. Variant chr15-27966775-G-A is described in ClinVar as [Benign]. Clinvar id is 255722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-27966775-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=2.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OCA2	NM_000275.3	c.1551C>T	p.Cys517=	synonymous_variant	15/24	ENST00000354638.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCA2	ENST00000354638.8	c.1551C>T	p.Cys517=	synonymous_variant	15/24	1	NM_000275.3	P1
OCA2	ENST00000353809.9	c.1479C>T	p.Cys493=	synonymous_variant	14/23	1

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81461 AN: 151866 Hom.: 25301 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.532

GnomAD3 exomes AF: 0.555 AC: 139169 AN: 250936 Hom.: 44103 AF XY: 0.559 AC XY: 75785 AN XY: 135602

Gnomad AFR exome AF: 0.274

Gnomad AMR exome AF: 0.382

Gnomad ASJ exome AF: 0.595

Gnomad EAS exome AF: 0.147

Gnomad SAS exome AF: 0.379

Gnomad FIN exome AF: 0.743

Gnomad NFE exome AF: 0.718

Gnomad OTH exome AF: 0.605

GnomAD4 exome AF: 0.652 AC: 952314 AN: 1460656 Hom.: 326969 Cov.: 43 AF XY: 0.646 AC XY: 469183 AN XY: 726640

Gnomad4 AFR exome AF: 0.260

Gnomad4 AMR exome AF: 0.392

Gnomad4 ASJ exome AF: 0.597

Gnomad4 EAS exome AF: 0.118

Gnomad4 SAS exome AF: 0.386

Gnomad4 FIN exome AF: 0.744

Gnomad4 NFE exome AF: 0.713

Gnomad4 OTH exome AF: 0.608

GnomAD4 genome AF: 0.536 AC: 81464 AN: 151984 Hom.: 25293 Cov.: 32 AF XY: 0.531 AC XY: 39436 AN XY: 74288

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.596

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.744

Gnomad4 NFE AF: 0.716

Gnomad4 OTH AF: 0.529

Alfa AF: 0.630 Hom.: 25572

Bravo AF: 0.505

Asia WGS AF: 0.309 AC: 1076 AN: 3478

EpiCase AF: 0.692

EpiControl AF: 0.685

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 17, 2015	- -

Tyrosinase-positive oculocutaneous albinism Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	6.6
Dann	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs1800411; hg19: chr15-28211921; COSMIC: COSV62347205;