15-27755871-A-C

Variant names:

• chr15-27755871-A-C
• rs11074304
• NM_000275.3:c.2433-399T>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.2433-399T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 152,018 control chromosomes in the GnomAD database, including 24,456 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 0.56 (24456 hom., cov: 32)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 3 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.2433-399T>G		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.2433-399T>G		intron_variant	Intron 23 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.2361-399T>G		intron_variant	Intron 22 of 22	1		ENSP00000261276.8

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85678 AN: 151898 Hom.: 24439 Cov.: 32

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.564 AC: 85735 AN: 152018 Hom.: 24456 Cov.: 32 AF XY: 0.566 AC XY: 42035 AN XY: 74310

African (AFR) AF: 0.542 AC: 22464 AN: 41454

American (AMR) AF: 0.531 AC: 8109 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1547 AN: 3472

East Asian (EAS) AF: 0.638 AC: 3286 AN: 5148

South Asian (SAS) AF: 0.534 AC: 2574 AN: 4820

European-Finnish (FIN) AF: 0.642 AC: 6777 AN: 10562

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.581 AC: 39460 AN: 67966

Other (OTH) AF: 0.520 AC: 1097 AN: 2108

Alfa AF: 0.561 Hom.: 36019

Bravo AF: 0.556

Asia WGS AF: 0.622 AC: 2162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.87
DANN	Benign	0.36
PhyloP100		-1.1
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: rs11074304; hg19: chr15-28001017;