15-28090674-A-G

Variant names:

• chr15-28090674-A-G
• rs4778138
• NM_000275.3:c.-22+8550T>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.-22+8550T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 152,050 control chromosomes in the GnomAD database, including 11,876 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 0.32 (11876 hom., cov: 33)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 48 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.715 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.-22+8550T>C		intron	N/A	NP_000266.2
	OCA2	NM_001300984.2		c.-22+8550T>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.-22+8550T>C		intron	N/A	ENSP00000346659.3
	OCA2	ENST00000353809.9	TSL:1	c.-22+8550T>C		intron	N/A	ENSP00000261276.8
	OCA2	ENST00000431101.1	TSL:3	c.-22+8437T>C		intron	N/A	ENSP00000415431.1

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48141 AN: 151932 Hom.: 11829 Cov.: 33

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.0601

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.317 AC: 48239 AN: 152050 Hom.: 11876 Cov.: 33 AF XY: 0.321 AC XY: 23870 AN XY: 74348

African (AFR) AF: 0.638 AC: 26429 AN: 41438

American (AMR) AF: 0.278 AC: 4251 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 735 AN: 3470

East Asian (EAS) AF: 0.734 AC: 3789 AN: 5162

South Asian (SAS) AF: 0.442 AC: 2124 AN: 4808

European-Finnish (FIN) AF: 0.0601 AC: 637 AN: 10600

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9174 AN: 67980

Other (OTH) AF: 0.341 AC: 721 AN: 2112

Alfa AF: 0.213 Hom.: 22105

Bravo AF: 0.347

Asia WGS AF: 0.540 AC: 1878 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	2.2
DANN	Benign	0.30
PhyloP100		-1.3
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: rs4778138; hg19: chr15-28335820;