15-28090674-A-G

Position:

• chr15-28090674-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OCA2	NM_000275.3	c.-22+8550T>C		intron_variant		ENST00000354638.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCA2	ENST00000354638.8	c.-22+8550T>C		intron_variant		1	NM_000275.3	P1
OCA2	ENST00000353809.9	c.-22+8550T>C		intron_variant		1
OCA2	ENST00000431101.1	c.-22+8437T>C		intron_variant		3
OCA2	ENST00000445578.5	c.-22+8550T>C		intron_variant		3

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

Gnomad4 AFR AF: 0.638

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.734

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.0601

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.341

Alfa AF: 0.198 Hom.: 8060

Bravo AF: 0.347

Asia WGS AF: 0.540 AC: 1878 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.2
DANN	Benign	0.30

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

Publications

LitVar

Other links and lift over

dbSNP: rs4778138; hg19: chr15-28335820;