rs2871875

Variant names:

• chr15-28019708-A-G
• rs2871875
• NM_000275.3:c.647-1151T>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.647-1151T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 151,998 control chromosomes in the GnomAD database, including 31,244 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 0.62 (31244 hom., cov: 32)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• 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: 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.647-1151T>C		intron_variant	Intron 6 of 23	ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.647-1151T>C		intron_variant	Intron 6 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.647-1151T>C		intron_variant	Intron 6 of 22	1		ENSP00000261276.8
OCA2	ENST00000431101.1	c.647-1151T>C		intron_variant	Intron 6 of 6	3		ENSP00000415431.1
OCA2	ENST00000445578.5	c.574-3522T>C		intron_variant	Intron 5 of 5	3		ENSP00000414425.1

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93577 AN: 151884 Hom.: 31228 Cov.: 32

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.634

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

GnomAD4 genome AF: 0.616 AC: 93610 AN: 151998 Hom.: 31244 Cov.: 32 AF XY: 0.609 AC XY: 45260 AN XY: 74310

African (AFR) AF: 0.440 AC: 18228 AN: 41446

American (AMR) AF: 0.506 AC: 7729 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2373 AN: 3464

East Asian (EAS) AF: 0.209 AC: 1072 AN: 5120

South Asian (SAS) AF: 0.337 AC: 1621 AN: 4810

European-Finnish (FIN) AF: 0.791 AC: 8380 AN: 10594

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.765 AC: 51980 AN: 67960

Other (OTH) AF: 0.630 AC: 1330 AN: 2112

Alfa AF: 0.711 Hom.: 62534

Bravo AF: 0.590

Asia WGS AF: 0.399 AC: 1383 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.38
DANN	Benign	0.23
PhyloP100		-1.4
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: rs2871875; hg19: chr15-28264854;