rs17566952

chr15-27951739-C-Gchr15-27951739-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.1951+45G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0619 in 1,346,208 control chromosomes in the GnomAD database, including 3,369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.048 (255 hom., cov: 33)
  • Exomes 𝑓: 0.064 (3114 hom.)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.619

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=-0.82).
• BP6: Variant 15-27951739-C-G is Benign according to our data. Variant chr15-27951739-C-G is described in ClinVar as [Benign]. Clinvar id is 1262515.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OCA2	NM_000275.3	c.1951+45G>C		intron_variant		ENST00000354638.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCA2	ENST00000354638.8	c.1951+45G>C		intron_variant		1	NM_000275.3	P1
OCA2	ENST00000353809.9	c.1879+45G>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0479 AC: 7287 AN: 152176 Hom.: 254 Cov.: 33

Gnomad AFR AF: 0.0114

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.0650

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.00751

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0264

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0604

Gnomad OTH AF: 0.0650

GnomAD3 exomes AF: 0.0599 AC: 14348 AN: 239646 Hom.: 657 AF XY: 0.0661 AC XY: 8542 AN XY: 129178

Gnomad AFR exome AF: 0.00999

Gnomad AMR exome AF: 0.0357

Gnomad ASJ exome AF: 0.154

Gnomad EAS exome AF: 0.00626

Gnomad SAS exome AF: 0.124

Gnomad FIN exome AF: 0.0315

Gnomad NFE exome AF: 0.0623

Gnomad OTH exome AF: 0.0710

GnomAD4 exome AF: 0.0637 AC: 76007 AN: 1193914 Hom.: 3114 Cov.: 16 AF XY: 0.0665 AC XY: 40363 AN XY: 606538

Gnomad4 AFR exome AF: 0.00903

Gnomad4 AMR exome AF: 0.0380

Gnomad4 ASJ exome AF: 0.152

Gnomad4 EAS exome AF: 0.00455

Gnomad4 SAS exome AF: 0.129

Gnomad4 FIN exome AF: 0.0308

Gnomad4 NFE exome AF: 0.0623

Gnomad4 OTH exome AF: 0.0675

GnomAD4 genome AF: 0.0478 AC: 7284 AN: 152294 Hom.: 255 Cov.: 33 AF XY: 0.0491 AC XY: 3656 AN XY: 74454

Gnomad4 AFR AF: 0.0114

Gnomad4 AMR AF: 0.0649

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.00753

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.0264

Gnomad4 NFE AF: 0.0604

Gnomad4 OTH AF: 0.0643

Alfa AF: 0.0440 Hom.: 63

Bravo AF: 0.0466

Asia WGS AF: 0.0500 AC: 172 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 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.37
Dann	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17566952; hg19: chr15-28196885; COSMIC: COSV62347680;