15-28083619-G-A

Variant names:

• chr15-28083619-G-A
• rs7174027
• NM_000275.3:c.-21-1724C>T

Variant summary

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

The NM_000275.3(OCA2):​c.-21-1724C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,142 control chromosomes in the GnomAD database, including 6,700 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 0.24 (6700 hom., cov: 33)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.973
• Publications: 17 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	NM_000275.3	MANE Select	c.-21-1724C>T		intron	N/A	NP_000266.2
	OCA2	NM_001300984.2		c.-21-1724C>T		intron	N/A	NP_001287913.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	ENST00000354638.8	TSL:1 MANE Select	c.-21-1724C>T		intron	N/A	ENSP00000346659.3
	OCA2	ENST00000353809.9	TSL:1	c.-21-1724C>T		intron	N/A	ENSP00000261276.8
	OCA2	ENST00000431101.1	TSL:3	c.-21-1724C>T		intron	N/A	ENSP00000415431.1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36224 AN: 152024 Hom.: 6692 Cov.: 33

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.0578

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.238 AC: 36277 AN: 152142 Hom.: 6700 Cov.: 33 AF XY: 0.243 AC XY: 18052 AN XY: 74410

African (AFR) AF: 0.444 AC: 18436 AN: 41500

American (AMR) AF: 0.219 AC: 3343 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 658 AN: 3470

East Asian (EAS) AF: 0.717 AC: 3700 AN: 5162

South Asian (SAS) AF: 0.359 AC: 1732 AN: 4820

European-Finnish (FIN) AF: 0.0578 AC: 613 AN: 10600

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6879 AN: 67996

Other (OTH) AF: 0.264 AC: 556 AN: 2108

Alfa AF: 0.156 Hom.: 12957

Bravo AF: 0.260

Asia WGS AF: 0.485 AC: 1685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.49
DANN	Benign	0.44
PhyloP100		-0.97
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: rs7174027; hg19: chr15-28328765;