XM_017022258.2:c.2457-32773C>T

Variant names:

• chr15-27752101-G-A
• rs17565841
• XM_017022258.2:c.2457-32773C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_017022258.2(OCA2):​c.2457-32773C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,236 control chromosomes in the GnomAD database, including 890 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 0.10 (890 hom., cov: 33)
• Consequence: OCA2 XM_017022258.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	XM_017022258.2	c.2457-32773C>T		intron_variant	Intron 23 of 23		XP_016877747.1
OCA2	XM_047432606.1	c.2433-32773C>T		intron_variant	Intron 23 of 23		XP_047288562.1
OCA2	XM_047432607.1	c.2385-32773C>T		intron_variant	Intron 22 of 22		XP_047288563.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15588 AN: 152118 Hom.: 889 Cov.: 33

Gnomad AFR AF: 0.0646

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.0840

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0858

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.102 AC: 15601 AN: 152236 Hom.: 890 Cov.: 33 AF XY: 0.103 AC XY: 7664 AN XY: 74428

African (AFR) AF: 0.0645 AC: 2681 AN: 41540

American (AMR) AF: 0.142 AC: 2164 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 624 AN: 3468

East Asian (EAS) AF: 0.0844 AC: 437 AN: 5178

South Asian (SAS) AF: 0.150 AC: 723 AN: 4824

European-Finnish (FIN) AF: 0.0858 AC: 910 AN: 10612

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7548 AN: 68004

Other (OTH) AF: 0.131 AC: 277 AN: 2112

Alfa AF: 0.108 Hom.: 1927

Bravo AF: 0.106

Asia WGS AF: 0.0990 AC: 344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.11
DANN	Benign	0.84
PhyloP100		-2.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17565841; hg19: chr15-27997247;