NM_000275.3:c.2432+12945A>G

Variant names:

• chr15-27832014-T-C
• rs4778190
• NM_000275.3:c.2432+12945A>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.2432+12945A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 150,914 control chromosomes in the GnomAD database, including 44,007 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 0.75 (44007 hom., cov: 27)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.85
• 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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.2432+12945A>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.2432+12945A>G		intron_variant	Intron 23 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.2360+12945A>G		intron_variant	Intron 22 of 22	1		ENSP00000261276.8

Frequencies

GnomAD3 genomes AF: 0.751 AC: 113280 AN: 150796 Hom.: 43951 Cov.: 27

Gnomad AFR AF: 0.899

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.886

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.846

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.815

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

GnomAD4 genome AF: 0.751 AC: 113396 AN: 150914 Hom.: 44007 Cov.: 27 AF XY: 0.754 AC XY: 55523 AN XY: 73608

African (AFR) AF: 0.899 AC: 36939 AN: 41088

American (AMR) AF: 0.813 AC: 12362 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 2714 AN: 3466

East Asian (EAS) AF: 0.997 AC: 4993 AN: 5006

South Asian (SAS) AF: 0.886 AC: 4197 AN: 4738

European-Finnish (FIN) AF: 0.574 AC: 5982 AN: 10430

Middle Eastern (MID) AF: 0.838 AC: 243 AN: 290

European-Non Finnish (NFE) AF: 0.643 AC: 43550 AN: 67688

Other (OTH) AF: 0.817 AC: 1715 AN: 2100

Alfa AF: 0.495 Hom.: 1070

Bravo AF: 0.776

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.28
PhyloP100		-2.9
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: rs4778190; hg19: chr15-28077160;