15-27941839-G-C

Variant names:

• chr15-27941839-G-C
• rs2594938
• NM_000275.3:c.1951+9945C>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.1951+9945C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 152,068 control chromosomes in the GnomAD database, including 11,230 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 0.34 (11230 hom., cov: 33)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.596
• 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: ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.589 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	NM_000275.3	MANE Select	c.1951+9945C>G		intron	N/A	NP_000266.2	Q04671-1
	OCA2	NM_001300984.2		c.1879+9945C>G		intron	N/A	NP_001287913.1	Q04671-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	ENST00000354638.8	TSL:1 MANE Select	c.1951+9945C>G		intron	N/A	ENSP00000346659.3	Q04671-1
	OCA2	ENST00000353809.9	TSL:1	c.1879+9945C>G		intron	N/A	ENSP00000261276.8	Q04671-2
	OCA2	ENST00000910120.1		c.1951+9945C>G		intron	N/A	ENSP00000580179.1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51574 AN: 151950 Hom.: 11197 Cov.: 33

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.0121

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.340 AC: 51668 AN: 152068 Hom.: 11230 Cov.: 33 AF XY: 0.341 AC XY: 25369 AN XY: 74342

African (AFR) AF: 0.596 AC: 24704 AN: 41476

American (AMR) AF: 0.360 AC: 5508 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 983 AN: 3468

East Asian (EAS) AF: 0.0122 AC: 63 AN: 5178

South Asian (SAS) AF: 0.495 AC: 2388 AN: 4820

European-Finnish (FIN) AF: 0.197 AC: 2079 AN: 10556

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14971 AN: 67964

Other (OTH) AF: 0.328 AC: 692 AN: 2112

Alfa AF: 0.126 Hom.: 199

Bravo AF: 0.352

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.68
DANN	Benign	0.53
PhyloP100		-0.60
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: rs2594938; hg19: chr15-28186985;