NM_000275.3:c.228-4456G>A

Variant names:

• chr15-28036619-C-T
• rs4778232
• NM_000275.3:c.228-4456G>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.228-4456G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 152,008 control chromosomes in the GnomAD database, including 18,223 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 0.42 (18223 hom., cov: 32)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22
• Publications: 9 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000275.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	NM_000275.3	MANE Select	c.228-4456G>A		intron	N/A	NP_000266.2
	OCA2	NM_001300984.2		c.228-4456G>A		intron	N/A	NP_001287913.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	ENST00000354638.8	TSL:1 MANE Select	c.228-4456G>A		intron	N/A	ENSP00000346659.3
	OCA2	ENST00000353809.9	TSL:1	c.228-4456G>A		intron	N/A	ENSP00000261276.8
	OCA2	ENST00000431101.1	TSL:3	c.228-4456G>A		intron	N/A	ENSP00000415431.1

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63715 AN: 151890 Hom.: 18175 Cov.: 32

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.420 AC: 63825 AN: 152008 Hom.: 18223 Cov.: 32 AF XY: 0.423 AC XY: 31444 AN XY: 74326

African (AFR) AF: 0.763 AC: 31647 AN: 41460

American (AMR) AF: 0.393 AC: 5993 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1254 AN: 3468

East Asian (EAS) AF: 0.898 AC: 4628 AN: 5152

South Asian (SAS) AF: 0.444 AC: 2141 AN: 4818

European-Finnish (FIN) AF: 0.180 AC: 1904 AN: 10586

Middle Eastern (MID) AF: 0.503 AC: 147 AN: 292

European-Non Finnish (NFE) AF: 0.221 AC: 15034 AN: 67960

Other (OTH) AF: 0.434 AC: 916 AN: 2112

Alfa AF: 0.306 Hom.: 28880

Bravo AF: 0.452

Asia WGS AF: 0.654 AC: 2273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.10
DANN	Benign	0.26
PhyloP100		-2.2
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: rs4778232; hg19: chr15-28281765;