chr15-27871136-T-C

Variant names:

• chr15-27871136-T-C
• rs41304383
• NM_000275.3:c.2244+18A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000275.3(OCA2):​c.2244+18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0393 in 1,592,268 control chromosomes in the GnomAD database, including 1,436 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (124 hom., cov: 33)
  • Exomes 𝑓: 0.039 (1312 hom.)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.849
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 15-27871136-T-C is Benign according to our data. Variant chr15-27871136-T-C is described in ClinVar as Benign. ClinVar VariationId is 195558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.2244+18A>G		intron_variant	Intron 21 of 23	ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.2244+18A>G		intron_variant	Intron 21 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.2172+18A>G		intron_variant	Intron 20 of 22	1		ENSP00000261276.8

Frequencies

GnomAD3 genomes AF: 0.0381 AC: 5800 AN: 152122 Hom.: 124 Cov.: 33

Gnomad AFR AF: 0.0436

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0295

Gnomad ASJ AF: 0.0289

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0607

Gnomad FIN AF: 0.0264

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0401

Gnomad OTH AF: 0.0489

GnomAD2 exomes AF: 0.0372 AC: 9345 AN: 251064 AF XY: 0.0397

Gnomad AFR exome AF: 0.0439

Gnomad AMR exome AF: 0.0187

Gnomad ASJ exome AF: 0.0317

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0282

Gnomad NFE exome AF: 0.0418

Gnomad OTH exome AF: 0.0426

GnomAD4 exome AF: 0.0395 AC: 56814 AN: 1440028 Hom.: 1312 Cov.: 29 AF XY: 0.0406 AC XY: 29105 AN XY: 717664

African (AFR) AF: 0.0410 AC: 1351 AN: 32944

American (AMR) AF: 0.0200 AC: 894 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.0275 AC: 716 AN: 26026

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39610

South Asian (SAS) AF: 0.0677 AC: 5811 AN: 85794

European-Finnish (FIN) AF: 0.0321 AC: 1712 AN: 53388

Middle Eastern (MID) AF: 0.0759 AC: 436 AN: 5748

European-Non Finnish (NFE) AF: 0.0398 AC: 43451 AN: 1092120

Other (OTH) AF: 0.0408 AC: 2439 AN: 59712

GnomAD4 genome AF: 0.0381 AC: 5798 AN: 152240 Hom.: 124 Cov.: 33 AF XY: 0.0370 AC XY: 2752 AN XY: 74428

African (AFR) AF: 0.0436 AC: 1812 AN: 41548

American (AMR) AF: 0.0295 AC: 451 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0289 AC: 100 AN: 3466

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5172

South Asian (SAS) AF: 0.0600 AC: 289 AN: 4820

European-Finnish (FIN) AF: 0.0264 AC: 280 AN: 10610

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0401 AC: 2728 AN: 68010

Other (OTH) AF: 0.0474 AC: 100 AN: 2108

Alfa AF: 0.0409 Hom.: 54

Bravo AF: 0.0386

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 28, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:2

Dec 18, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.41
DANN	Benign	0.27
PhyloP100		-0.85
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: rs41304383; hg19: chr15-28116282;