rs11858340

Positions:

• chr15-27835438-A-G
• chr15-27835438-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000275.3(OCA2):​c.2432+9521T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 152,128 control chromosomes in the GnomAD database, including 35,287 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 0.67 (35287 hom., cov: 33)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OCA2	NM_000275.3	c.2432+9521T>C		intron_variant		ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.2432+9521T>C		intron_variant		1	NM_000275.3	ENSP00000346659	P1
OCA2	ENST00000353809.9	c.2360+9521T>C		intron_variant		1		ENSP00000261276

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101680 AN: 152010 Hom.: 35231 Cov.: 33

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.961

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.727

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

GnomAD4 genome AF: 0.669 AC: 101796 AN: 152128 Hom.: 35287 Cov.: 33 AF XY: 0.671 AC XY: 49870 AN XY: 74354

Gnomad4 AFR AF: 0.816

Gnomad4 AMR AF: 0.693

Gnomad4 ASJ AF: 0.674

Gnomad4 EAS AF: 0.961

Gnomad4 SAS AF: 0.751

Gnomad4 FIN AF: 0.493

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.729

Alfa AF: 0.605 Hom.: 4908

Bravo AF: 0.691

Asia WGS AF: 0.862 AC: 3000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.55

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: rs11858340; hg19: chr15-28080584;