rs12592271

Positions:

• chr15-27844776-C-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.2432+183G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,152 control chromosomes in the GnomAD database, including 4,161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (4161 hom., cov: 32)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.485

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=-0.89).
• BP6: Variant 15-27844776-C-T is Benign according to our data. Variant chr15-27844776-C-T is described in ClinVar as [Benign]. Clinvar id is 1257060.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OCA2	NM_000275.3	c.2432+183G>A		intron_variant		ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.2432+183G>A		intron_variant		1	NM_000275.3	ENSP00000346659	P1
OCA2	ENST00000353809.9	c.2360+183G>A		intron_variant		1		ENSP00000261276

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31805 AN: 152034 Hom.: 4158 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.210

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.209 AC: 31825 AN: 152152 Hom.: 4161 Cov.: 32 AF XY: 0.219 AC XY: 16262 AN XY: 74380

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.562

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.211

Alfa AF: 0.195 Hom.: 427

Bravo AF: 0.214

Asia WGS AF: 0.416 AC: 1445 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	-0.89
CADD	Benign	4.7
DANN	Benign	0.85

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: rs12592271; hg19: chr15-28089922;