15-27908182-T-C

Variant names:

• chr15-27908182-T-C
• rs2703922
• NM_000275.3:c.2079+17945A>G

Variant summary

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

The NM_000275.3(OCA2):​c.2079+17945A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 151,894 control chromosomes in the GnomAD database, including 31,111 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 0.63 (31111 hom., cov: 32)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214
• 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: ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

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 (EAS) allele frequency at 95% confidence interval = 0.942 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	NM_000275.3	MANE Select	c.2079+17945A>G		intron	N/A	NP_000266.2	Q04671-1
	OCA2	NM_001300984.2		c.2007+17945A>G		intron	N/A	NP_001287913.1	Q04671-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	ENST00000354638.8	TSL:1 MANE Select	c.2079+17945A>G		intron	N/A	ENSP00000346659.3	Q04671-1
	OCA2	ENST00000353809.9	TSL:1	c.2007+17945A>G		intron	N/A	ENSP00000261276.8	Q04671-2
	OCA2	ENST00000910120.1		c.2079+17945A>G		intron	N/A	ENSP00000580179.1

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96181 AN: 151776 Hom.: 31088 Cov.: 32

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.964

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.796

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.703

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

GnomAD4 genome AF: 0.634 AC: 96246 AN: 151894 Hom.: 31111 Cov.: 32 AF XY: 0.638 AC XY: 47397 AN XY: 74262

African (AFR) AF: 0.619 AC: 25604 AN: 41390

American (AMR) AF: 0.738 AC: 11275 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 2720 AN: 3472

East Asian (EAS) AF: 0.964 AC: 4994 AN: 5180

South Asian (SAS) AF: 0.555 AC: 2672 AN: 4812

European-Finnish (FIN) AF: 0.586 AC: 6164 AN: 10524

Middle Eastern (MID) AF: 0.791 AC: 231 AN: 292

European-Non Finnish (NFE) AF: 0.596 AC: 40452 AN: 67926

Other (OTH) AF: 0.706 AC: 1492 AN: 2112

Alfa AF: 0.464 Hom.: 1237

Bravo AF: 0.652

Asia WGS AF: 0.736 AC: 2545 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.1
DANN	Benign	0.47
PhyloP100		0.21
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: rs2703922; hg19: chr15-28153328;