chr15-27835546-T-C

Position:

• chr15-27835546-T-C

Variant summary

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

The NM_000275.3(OCA2):​c.2432+9413A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 152,158 control chromosomes in the GnomAD database, including 34,531 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 0.66 (34531 hom., cov: 34)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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 = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OCA2	NM_000275.3	c.2432+9413A>G		intron_variant		ENST00000354638.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCA2	ENST00000354638.8	c.2432+9413A>G		intron_variant		1	NM_000275.3	P1
OCA2	ENST00000353809.9	c.2360+9413A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100488 AN: 152038 Hom.: 34478 Cov.: 34

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.959

Gnomad SAS AF: 0.745

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.720

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

GnomAD4 genome AF: 0.661 AC: 100601 AN: 152158 Hom.: 34531 Cov.: 34 AF XY: 0.662 AC XY: 49262 AN XY: 74388

Gnomad4 AFR AF: 0.815

Gnomad4 AMR AF: 0.647

Gnomad4 ASJ AF: 0.668

Gnomad4 EAS AF: 0.959

Gnomad4 SAS AF: 0.746

Gnomad4 FIN AF: 0.490

Gnomad4 NFE AF: 0.567

Gnomad4 OTH AF: 0.722

Alfa AF: 0.600 Hom.: 55725

Bravo AF: 0.679

Asia WGS AF: 0.856 AC: 2979 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.19
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: rs11852452; hg19: chr15-28080692;