15-28049776-G-T

Variant names:

• chr15-28049776-G-T
• rs1597196
• NM_000275.3:c.228-17613C>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.228-17613C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,038 control chromosomes in the GnomAD database, including 13,065 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 0.35 (13065 hom., cov: 32)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 10 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.228-17613C>A		intron_variant	Intron 2 of 23	ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.228-17613C>A		intron_variant	Intron 2 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.228-17613C>A		intron_variant	Intron 2 of 22	1		ENSP00000261276.8
OCA2	ENST00000431101.1	c.228-17613C>A		intron_variant	Intron 2 of 6	3		ENSP00000415431.1
OCA2	ENST00000445578.5	c.228-17613C>A		intron_variant	Intron 2 of 5	3		ENSP00000414425.1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52619 AN: 151920 Hom.: 13013 Cov.: 32

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.347 AC: 52737 AN: 152038 Hom.: 13065 Cov.: 32 AF XY: 0.346 AC XY: 25704 AN XY: 74322

African (AFR) AF: 0.705 AC: 29205 AN: 41436

American (AMR) AF: 0.328 AC: 5015 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1018 AN: 3466

East Asian (EAS) AF: 0.227 AC: 1173 AN: 5168

South Asian (SAS) AF: 0.308 AC: 1484 AN: 4812

European-Finnish (FIN) AF: 0.147 AC: 1558 AN: 10580

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12294 AN: 67988

Other (OTH) AF: 0.351 AC: 739 AN: 2108

Alfa AF: 0.233 Hom.: 21538

Bravo AF: 0.376

Asia WGS AF: 0.349 AC: 1214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.62
DANN	Benign	0.43
PhyloP100		-1.3
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: rs1597196; hg19: chr15-28294922;