rs728405

Variant names:

• chr15-27954707-C-A
• rs728405
• NM_000275.3:c.1842+451G>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.1842+451G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 147,638 control chromosomes in the GnomAD database, including 28,378 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 0.58 (28378 hom., cov: 27)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 9 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.1842+451G>T		intron_variant	Intron 17 of 23	ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.1842+451G>T		intron_variant	Intron 17 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.1770+451G>T		intron_variant	Intron 16 of 22	1		ENSP00000261276.8

Frequencies

GnomAD3 genomes AF: 0.583 AC: 86022 AN: 147562 Hom.: 28392 Cov.: 27

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.866

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.583 AC: 86010 AN: 147638 Hom.: 28378 Cov.: 27 AF XY: 0.575 AC XY: 41269 AN XY: 71806

African (AFR) AF: 0.335 AC: 13633 AN: 40680

American (AMR) AF: 0.489 AC: 7327 AN: 14990

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2495 AN: 3432

East Asian (EAS) AF: 0.136 AC: 698 AN: 5140

South Asian (SAS) AF: 0.440 AC: 2083 AN: 4730

European-Finnish (FIN) AF: 0.728 AC: 6599 AN: 9062

Middle Eastern (MID) AF: 0.710 AC: 196 AN: 276

European-Non Finnish (NFE) AF: 0.768 AC: 51019 AN: 66396

Other (OTH) AF: 0.581 AC: 1181 AN: 2032

Alfa AF: 0.675 Hom.: 19922

Bravo AF: 0.563

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.062
DANN	Benign	0.35
PhyloP100		-1.7
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: rs728405; hg19: chr15-28199853;