NM_000275.3:c.-21-794G>C

Variant names:

• chr15-28082689-C-G
• rs4778137
• NM_000275.3:c.-21-794G>C

Variant summary

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

The NM_000275.3(OCA2):​c.-21-794G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,052 control chromosomes in the GnomAD database, including 14,838 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 0.41 (14838 hom., cov: 33)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• Publications: 13 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.804 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.-21-794G>C		intron	N/A	NP_000266.2
	OCA2	NM_001300984.2		c.-21-794G>C		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.-21-794G>C		intron	N/A	ENSP00000346659.3
	OCA2	ENST00000353809.9	TSL:1	c.-21-794G>C		intron	N/A	ENSP00000261276.8
	OCA2	ENST00000431101.1	TSL:3	c.-21-794G>C		intron	N/A	ENSP00000415431.1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62675 AN: 151934 Hom.: 14820 Cov.: 33

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.413 AC: 62752 AN: 152052 Hom.: 14838 Cov.: 33 AF XY: 0.413 AC XY: 30708 AN XY: 74318

African (AFR) AF: 0.597 AC: 24735 AN: 41442

American (AMR) AF: 0.429 AC: 6553 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1423 AN: 3470

East Asian (EAS) AF: 0.825 AC: 4265 AN: 5170

South Asian (SAS) AF: 0.452 AC: 2177 AN: 4812

European-Finnish (FIN) AF: 0.182 AC: 1924 AN: 10578

Middle Eastern (MID) AF: 0.568 AC: 166 AN: 292

European-Non Finnish (NFE) AF: 0.299 AC: 20304 AN: 67990

Other (OTH) AF: 0.441 AC: 928 AN: 2106

Alfa AF: 0.162 Hom.: 235

Bravo AF: 0.442

Asia WGS AF: 0.622 AC: 2163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.26
DANN	Benign	0.49
PhyloP100		-1.5
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: rs4778137; hg19: chr15-28327835;