15-28021089-T-C

Variant names:

• chr15-28021089-T-C
• rs746861
• NM_000275.3:c.646+1412A>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.646+1412A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 152,084 control chromosomes in the GnomAD database, including 15,295 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 0.44 (15295 hom., cov: 33)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.312
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.646+1412A>G		intron_variant	Intron 6 of 23	ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.646+1412A>G		intron_variant	Intron 6 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.646+1412A>G		intron_variant	Intron 6 of 22	1		ENSP00000261276.8
OCA2	ENST00000431101.1	c.646+1412A>G		intron_variant	Intron 6 of 6	3		ENSP00000415431.1
OCA2	ENST00000445578.5	c.573+3756A>G		intron_variant	Intron 5 of 5	3		ENSP00000414425.1

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67186 AN: 151966 Hom.: 15283 Cov.: 33

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.442 AC: 67220 AN: 152084 Hom.: 15295 Cov.: 33 AF XY: 0.437 AC XY: 32512 AN XY: 74324

African (AFR) AF: 0.367 AC: 15235 AN: 41488

American (AMR) AF: 0.450 AC: 6873 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2056 AN: 3464

East Asian (EAS) AF: 0.269 AC: 1393 AN: 5180

South Asian (SAS) AF: 0.331 AC: 1594 AN: 4814

European-Finnish (FIN) AF: 0.449 AC: 4736 AN: 10548

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33607 AN: 67980

Other (OTH) AF: 0.500 AC: 1058 AN: 2116

Alfa AF: 0.480 Hom.: 31945

Bravo AF: 0.444

Asia WGS AF: 0.394 AC: 1368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.55
PhyloP100		0.31
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: rs746861; hg19: chr15-28266235;