NM_000275.3:c.2432+14955C>T

Variant names:

• chr15-27830004-G-A
• rs7183532
• NM_000275.3:c.2432+14955C>T

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+14955C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 151,992 control chromosomes in the GnomAD database, including 2,483 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 0.15 (2483 hom., cov: 33)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710
• Publications: 3 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.2432+14955C>T		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+14955C>T		intron_variant	Intron 23 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.2360+14955C>T		intron_variant	Intron 22 of 22	1		ENSP00000261276.8

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22452 AN: 151874 Hom.: 2476 Cov.: 33

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.0653

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.148 AC: 22498 AN: 151992 Hom.: 2483 Cov.: 33 AF XY: 0.153 AC XY: 11340 AN XY: 74270

African (AFR) AF: 0.235 AC: 9729 AN: 41442

American (AMR) AF: 0.180 AC: 2745 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 412 AN: 3470

East Asian (EAS) AF: 0.538 AC: 2774 AN: 5160

South Asian (SAS) AF: 0.116 AC: 560 AN: 4822

European-Finnish (FIN) AF: 0.131 AC: 1383 AN: 10552

Middle Eastern (MID) AF: 0.0890 AC: 26 AN: 292

European-Non Finnish (NFE) AF: 0.0653 AC: 4437 AN: 67970

Other (OTH) AF: 0.142 AC: 299 AN: 2108

Alfa AF: 0.0948 Hom.: 2068

Bravo AF: 0.161

Asia WGS AF: 0.317 AC: 1103 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
DANN	Benign	0.53
PhyloP100		-0.071
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: rs7183532; hg19: chr15-28075150;