chr15-27804158-A-G

Variant names:

• chr15-27804158-A-G
• rs6497235
• NM_000275.3:c.2432+40801T>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.2432+40801T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 152,040 control chromosomes in the GnomAD database, including 23,480 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 0.55 (23480 hom., cov: 33)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 5 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.2432+40801T>C		intron_variant	Intron 23 of 23	ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.2432+40801T>C		intron_variant	Intron 23 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.2360+40801T>C		intron_variant	Intron 22 of 22	1		ENSP00000261276.8

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83645 AN: 151922 Hom.: 23482 Cov.: 33

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.550 AC: 83675 AN: 152040 Hom.: 23480 Cov.: 33 AF XY: 0.551 AC XY: 40998 AN XY: 74346

African (AFR) AF: 0.521 AC: 21581 AN: 41442

American (AMR) AF: 0.604 AC: 9223 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 2271 AN: 3466

East Asian (EAS) AF: 0.461 AC: 2381 AN: 5168

South Asian (SAS) AF: 0.764 AC: 3685 AN: 4824

European-Finnish (FIN) AF: 0.425 AC: 4496 AN: 10572

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37952 AN: 67992

Other (OTH) AF: 0.620 AC: 1306 AN: 2108

Alfa AF: 0.557 Hom.: 56067

Bravo AF: 0.556

Asia WGS AF: 0.601 AC: 2090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.72
DANN	Benign	0.51
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: rs6497235; hg19: chr15-28049304;