rs1900758

chr15-27984951-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.1364+113G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 1,282,724 control chromosomes in the GnomAD database, including 261,509 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (22736 hom., cov: 33)
  • Exomes 𝑓: 0.62 (238773 hom.)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0900

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=-0.83).
• BP6: Variant 15-27984951-C-T is Benign according to our data. Variant chr15-27984951-C-T is described in ClinVar as [Benign]. Clinvar id is 1233186.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OCA2	NM_000275.3	c.1364+113G>A		intron_variant		ENST00000354638.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCA2	ENST00000354638.8	c.1364+113G>A		intron_variant		1	NM_000275.3	P1
OCA2	ENST00000353809.9	c.1292+113G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73997 AN: 152008 Hom.: 22742 Cov.: 33

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.0348

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.492

GnomAD4 exome AF: 0.624 AC: 705134 AN: 1130598 Hom.: 238773 AF XY: 0.615 AC XY: 352097 AN XY: 572276

Gnomad4 AFR exome AF: 0.171

Gnomad4 AMR exome AF: 0.302

Gnomad4 ASJ exome AF: 0.576

Gnomad4 EAS exome AF: 0.0209

Gnomad4 SAS exome AF: 0.314

Gnomad4 FIN exome AF: 0.708

Gnomad4 NFE exome AF: 0.705

Gnomad4 OTH exome AF: 0.572

GnomAD4 genome AF: 0.486 AC: 73975 AN: 152126 Hom.: 22736 Cov.: 33 AF XY: 0.479 AC XY: 35590 AN XY: 74368

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.380

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.0348

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.700

Gnomad4 NFE AF: 0.704

Gnomad4 OTH AF: 0.487

Alfa AF: 0.613 Hom.: 5409

Bravo AF: 0.452

Asia WGS AF: 0.184 AC: 645 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

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.4
Dann	Benign	0.63

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: rs1900758; hg19: chr15-28230097; COSMIC: COSV62344991;