NM_000275.3:c.2079+145T>C

Variant names:

• chr15-27925982-A-G
• rs3751651
• NM_000275.3:c.2079+145T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000275.3(OCA2):​c.2079+145T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 948,656 control chromosomes in the GnomAD database, including 32,568 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4975 hom., cov: 34)
  • Exomes 𝑓: 0.24 (27593 hom.)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.659
• Publications: 4 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: ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 15-27925982-A-G is Benign according to our data. Variant chr15-27925982-A-G is described in ClinVar as Benign. ClinVar VariationId is 1279773.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000275.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	NM_000275.3	MANE Select	c.2079+145T>C		intron	N/A	NP_000266.2	Q04671-1
	OCA2	NM_001300984.2		c.2007+145T>C		intron	N/A	NP_001287913.1	Q04671-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	ENST00000354638.8	TSL:1 MANE Select	c.2079+145T>C		intron	N/A	ENSP00000346659.3	Q04671-1
	OCA2	ENST00000353809.9	TSL:1	c.2007+145T>C		intron	N/A	ENSP00000261276.8	Q04671-2
	OCA2	ENST00000910120.1		c.2079+145T>C		intron	N/A	ENSP00000580179.1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35823 AN: 152104 Hom.: 4966 Cov.: 34

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.232

GnomAD4 exome AF: 0.238 AC: 189718 AN: 796434 Hom.: 27593 AF XY: 0.240 AC XY: 98271 AN XY: 409652

African (AFR) AF: 0.188 AC: 3460 AN: 18356

American (AMR) AF: 0.418 AC: 10163 AN: 24308

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 5785 AN: 17650

East Asian (EAS) AF: 0.676 AC: 22441 AN: 33216

South Asian (SAS) AF: 0.306 AC: 17137 AN: 56076

European-Finnish (FIN) AF: 0.232 AC: 10593 AN: 45730

Middle Eastern (MID) AF: 0.257 AC: 698 AN: 2718

European-Non Finnish (NFE) AF: 0.196 AC: 110049 AN: 561150

Other (OTH) AF: 0.252 AC: 9392 AN: 37230

GnomAD4 genome AF: 0.236 AC: 35864 AN: 152222 Hom.: 4975 Cov.: 34 AF XY: 0.244 AC XY: 18189 AN XY: 74412

African (AFR) AF: 0.188 AC: 7790 AN: 41520

American (AMR) AF: 0.348 AC: 5317 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1108 AN: 3472

East Asian (EAS) AF: 0.621 AC: 3219 AN: 5182

South Asian (SAS) AF: 0.302 AC: 1459 AN: 4830

European-Finnish (FIN) AF: 0.255 AC: 2695 AN: 10582

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13293 AN: 68018

Other (OTH) AF: 0.235 AC: 497 AN: 2114

Alfa AF: 0.221 Hom.: 11272

Bravo AF: 0.245

Asia WGS AF: 0.428 AC: 1488 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.4
DANN	Benign	0.71
PhyloP100		-0.66
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: rs3751651; hg19: chr15-28171128;