rs749846

Variant names:

• chr15-28023844-C-A
• rs749846
• NM_000275.3:c.573+1001G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-28023844-C-A
• chr15-28023844-C-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.573+1001G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 150,732 control chromosomes in the GnomAD database, including 4,851 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 0.21 (4851 hom., cov: 32)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.205
• Publications: 5 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.573+1001G>T		intron_variant	Intron 5 of 23	ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.573+1001G>T		intron_variant	Intron 5 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.573+1001G>T		intron_variant	Intron 5 of 22	1		ENSP00000261276.8
OCA2	ENST00000431101.1	c.573+1001G>T		intron_variant	Intron 5 of 6	3		ENSP00000415431.1
OCA2	ENST00000445578.5	c.573+1001G>T		intron_variant	Intron 5 of 5	3		ENSP00000414425.1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32105 AN: 150612 Hom.: 4861 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.321

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.213 AC: 32114 AN: 150732 Hom.: 4851 Cov.: 32 AF XY: 0.223 AC XY: 16429 AN XY: 73724

African (AFR) AF: 0.214 AC: 8783 AN: 41092

American (AMR) AF: 0.283 AC: 4291 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 686 AN: 3438

East Asian (EAS) AF: 0.873 AC: 4424 AN: 5068

South Asian (SAS) AF: 0.360 AC: 1708 AN: 4742

European-Finnish (FIN) AF: 0.156 AC: 1642 AN: 10548

Middle Eastern (MID) AF: 0.332 AC: 95 AN: 286

European-Non Finnish (NFE) AF: 0.146 AC: 9826 AN: 67384

Other (OTH) AF: 0.248 AC: 517 AN: 2082

Alfa AF: 0.167 Hom.: 324

Bravo AF: 0.224

Asia WGS AF: 0.526 AC: 1825 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.3
DANN	Benign	0.33
PhyloP100		0.20
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: rs749846; hg19: chr15-28268990;