rs7179994

Variant names:

• chr15-28078624-A-G
• rs7179994
• NM_000275.3:c.227+3024T>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.227+3024T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,120 control chromosomes in the GnomAD database, including 5,974 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 0.24 (5974 hom., cov: 32)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 7 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.227+3024T>C		intron_variant	Intron 2 of 23	ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.227+3024T>C		intron_variant	Intron 2 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.227+3024T>C		intron_variant	Intron 2 of 22	1		ENSP00000261276.8
OCA2	ENST00000431101.1	c.227+3024T>C		intron_variant	Intron 2 of 6	3		ENSP00000415431.1
OCA2	ENST00000445578.5	c.227+3024T>C		intron_variant	Intron 2 of 5	3		ENSP00000414425.1

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37078 AN: 152002 Hom.: 5964 Cov.: 32

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.244 AC: 37115 AN: 152120 Hom.: 5974 Cov.: 32 AF XY: 0.243 AC XY: 18047 AN XY: 74378

African (AFR) AF: 0.463 AC: 19211 AN: 41448

American (AMR) AF: 0.226 AC: 3450 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 736 AN: 3468

East Asian (EAS) AF: 0.249 AC: 1286 AN: 5174

South Asian (SAS) AF: 0.245 AC: 1183 AN: 4820

European-Finnish (FIN) AF: 0.119 AC: 1260 AN: 10616

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9254 AN: 68006

Other (OTH) AF: 0.245 AC: 517 AN: 2108

Alfa AF: 0.176 Hom.: 12817

Bravo AF: 0.262

Asia WGS AF: 0.282 AC: 979 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.66
DANN	Benign	0.49
PhyloP100		-1.2
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: rs7179994; hg19: chr15-28323770;