15-28026919-C-T

Variant names:

• chr15-28026919-C-T
• rs3794604
• NM_000275.3:c.515+952G>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.515+952G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,212 control chromosomes in the GnomAD database, including 1,197 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 0.11 (1197 hom., cov: 33)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.195
• Publications: 7 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.515+952G>A		intron_variant	Intron 4 of 23	ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.515+952G>A		intron_variant	Intron 4 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.515+952G>A		intron_variant	Intron 4 of 22	1		ENSP00000261276.8
OCA2	ENST00000431101.1	c.515+952G>A		intron_variant	Intron 4 of 6	3		ENSP00000415431.1
OCA2	ENST00000445578.5	c.515+952G>A		intron_variant	Intron 4 of 5	3		ENSP00000414425.1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16139 AN: 152094 Hom.: 1198 Cov.: 33

Gnomad AFR AF: 0.0263

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.106 AC: 16143 AN: 152212 Hom.: 1197 Cov.: 33 AF XY: 0.113 AC XY: 8413 AN XY: 74416

African (AFR) AF: 0.0262 AC: 1089 AN: 41546

American (AMR) AF: 0.207 AC: 3171 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 410 AN: 3466

East Asian (EAS) AF: 0.222 AC: 1143 AN: 5150

South Asian (SAS) AF: 0.216 AC: 1043 AN: 4822

European-Finnish (FIN) AF: 0.128 AC: 1354 AN: 10596

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.109 AC: 7445 AN: 68024

Other (OTH) AF: 0.145 AC: 307 AN: 2116

Alfa AF: 0.122 Hom.: 2290

Bravo AF: 0.108

Asia WGS AF: 0.228 AC: 789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.5
DANN	Benign	0.75
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3794604; hg19: chr15-28272065;