chr15-27752101-G-A

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.

Variant Effect in Transcripts

 

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

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 v4.9

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;