rs3751651

chr15-27925982-A-Gchr15-27925982-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000275.3(OCA2):c.2079+145T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 948,656 control chromosomes in the GnomAD database, including 32,568 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4975 hom., cov: 34)
  • Exomes 𝑓: 0.24 (27593 hom.)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.659

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 15-27925982-A-G is Benign according to our data. Variant chr15-27925982-A-G is described in ClinVar as [Benign]. Clinvar id is 1279773.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OCA2	NM_000275.3	c.2079+145T>C		intron_variant		ENST00000354638.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCA2	ENST00000354638.8	c.2079+145T>C		intron_variant		1	NM_000275.3	P1
OCA2	ENST00000353809.9	c.2007+145T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35823 AN: 152104 Hom.: 4966 Cov.: 34

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.232

GnomAD4 exome AF: 0.238 AC: 189718 AN: 796434 Hom.: 27593 AF XY: 0.240 AC XY: 98271 AN XY: 409652

Gnomad4 AFR exome AF: 0.188

Gnomad4 AMR exome AF: 0.418

Gnomad4 ASJ exome AF: 0.328

Gnomad4 EAS exome AF: 0.676

Gnomad4 SAS exome AF: 0.306

Gnomad4 FIN exome AF: 0.232

Gnomad4 NFE exome AF: 0.196

Gnomad4 OTH exome AF: 0.252

GnomAD4 genome AF: 0.236 AC: 35864 AN: 152222 Hom.: 4975 Cov.: 34 AF XY: 0.244 AC XY: 18189 AN XY: 74412

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.319

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.235

Alfa AF: 0.222 Hom.: 6836

Bravo AF: 0.245

Asia WGS AF: 0.428 AC: 1488 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	1.4
Dann	Benign	0.71

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: rs3751651; hg19: chr15-28171128;