rs7173419

chr15-27951675-T-C

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+109A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 821,232 control chromosomes in the GnomAD database, including 195,446 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.59 (30259 hom., cov: 32)
  • Exomes 𝑓: 0.68 (165187 hom.)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0710

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=-0.99).
• BP6: Variant 15-27951675-T-C is Benign according to our data. Variant chr15-27951675-T-C is described in ClinVar as [Benign]. Clinvar id is 1239793.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OCA2	NM_000275.3	c.1951+109A>G		intron_variant		ENST00000354638.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCA2	ENST00000354638.8	c.1951+109A>G		intron_variant		1	NM_000275.3	P1
OCA2	ENST00000353809.9	c.1879+109A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.594 AC: 90270 AN: 151932 Hom.: 30267 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.866

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.601

GnomAD4 exome AF: 0.677 AC: 453223 AN: 669182 Hom.: 165187 AF XY: 0.672 AC XY: 239468 AN XY: 356438

Gnomad4 AFR exome AF: 0.338

Gnomad4 AMR exome AF: 0.433

Gnomad4 ASJ exome AF: 0.743

Gnomad4 EAS exome AF: 0.0978

Gnomad4 SAS exome AF: 0.493

Gnomad4 FIN exome AF: 0.764

Gnomad4 NFE exome AF: 0.775

Gnomad4 OTH exome AF: 0.663

GnomAD4 genome AF: 0.594 AC: 90287 AN: 152050 Hom.: 30259 Cov.: 32 AF XY: 0.588 AC XY: 43720 AN XY: 74316

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.731

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.751

Gnomad4 NFE AF: 0.776

Gnomad4 OTH AF: 0.598

Alfa AF: 0.692 Hom.: 7284

Bravo AF: 0.564

Asia WGS AF: 0.338 AC: 1178 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	-0.99
Cadd	Benign	6.2
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: rs7173419; hg19: chr15-28196821; COSMIC: COSV62347676;