rs8037225

Variant names:

• chr15-27842301-C-T
• rs8037225
• NM_000275.3:c.2432+2658G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000275.3(OCA2):​c.2432+2658G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0988 in 152,168 control chromosomes in the GnomAD database, including 1,714 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.099 (1714 hom., cov: 33)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 1 publications found

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]

OCA2 Gene-Disease associations (from GenCC):

• oculocutaneous albinism type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.2432+2658G>A		intron_variant	Intron 23 of 23	ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.2432+2658G>A		intron_variant	Intron 23 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.2360+2658G>A		intron_variant	Intron 22 of 22	1		ENSP00000261276.8

Frequencies

GnomAD3 genomes AF: 0.0988 AC: 15016 AN: 152050 Hom.: 1713 Cov.: 33

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0358

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.0423

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.0125

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.0262

Gnomad OTH AF: 0.0755

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

GnomAD4 genome AF: 0.0988 AC: 15040 AN: 152168 Hom.: 1714 Cov.: 33 AF XY: 0.0986 AC XY: 7334 AN XY: 74390

African (AFR) AF: 0.268 AC: 11134 AN: 41486

American (AMR) AF: 0.0356 AC: 545 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3470

East Asian (EAS) AF: 0.0422 AC: 219 AN: 5184

South Asian (SAS) AF: 0.212 AC: 1021 AN: 4818

European-Finnish (FIN) AF: 0.0125 AC: 132 AN: 10590

Middle Eastern (MID) AF: 0.0240 AC: 7 AN: 292

European-Non Finnish (NFE) AF: 0.0262 AC: 1785 AN: 68010

Other (OTH) AF: 0.0757 AC: 160 AN: 2114

Alfa AF: 0.0730 Hom.: 133

Bravo AF: 0.102

Asia WGS AF: 0.170 AC: 591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.14
DANN	Benign	0.85
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8037225; hg19: chr15-28087447;