15-27906205-T-C

Variant names:

• chr15-27906205-T-C
• rs2044627
• NM_000275.3:c.2079+19922A>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.2079+19922A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 152,028 control chromosomes in the GnomAD database, including 11,510 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 0.39 (11510 hom., cov: 33)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.656
• Publications: 2 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=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.397 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.2079+19922A>G		intron	N/A	NP_000266.2
	OCA2	NM_001300984.2		c.2007+19922A>G		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.2079+19922A>G		intron	N/A	ENSP00000346659.3
	OCA2	ENST00000353809.9	TSL:1	c.2007+19922A>G		intron	N/A	ENSP00000261276.8

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58768 AN: 151908 Hom.: 11502 Cov.: 33

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.387 AC: 58803 AN: 152028 Hom.: 11510 Cov.: 33 AF XY: 0.383 AC XY: 28476 AN XY: 74308

African (AFR) AF: 0.386 AC: 16019 AN: 41456

American (AMR) AF: 0.394 AC: 6021 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1622 AN: 3470

East Asian (EAS) AF: 0.342 AC: 1769 AN: 5174

South Asian (SAS) AF: 0.261 AC: 1257 AN: 4824

European-Finnish (FIN) AF: 0.329 AC: 3478 AN: 10562

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27253 AN: 67942

Other (OTH) AF: 0.467 AC: 989 AN: 2116

Alfa AF: 0.376 Hom.: 1413

Bravo AF: 0.396

Asia WGS AF: 0.305 AC: 1061 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.5
DANN	Benign	0.37
PhyloP100		-0.66
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: rs2044627; hg19: chr15-28151351;