rs41304383

Positions:

• chr15-27871136-T-C

Variant summary

Our verdict is Benign. Variant got -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:4
• Conservation: PhyloP100: -0.849

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
OCA2	NM_000275.3	c.2244+18A>G		intron_variant		ENST00000354638.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCA2	ENST00000354638.8	c.2244+18A>G		intron_variant		1	NM_000275.3	P1
OCA2	ENST00000353809.9	c.2172+18A>G		intron_variant		1

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

GnomAD3 exomes AF: 0.0372 AC: 9345 AN: 251064 Hom.: 225 AF XY: 0.0397 AC XY: 5384 AN XY: 135724

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 SAS exome AF: 0.0671

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

Gnomad4 AFR exome AF: 0.0410

Gnomad4 AMR exome AF: 0.0200

Gnomad4 ASJ exome AF: 0.0275

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0677

Gnomad4 FIN exome AF: 0.0321

Gnomad4 NFE exome AF: 0.0398

Gnomad4 OTH exome AF: 0.0408

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

Gnomad4 AFR AF: 0.0436

Gnomad4 AMR AF: 0.0295

Gnomad4 ASJ AF: 0.0289

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0600

Gnomad4 FIN AF: 0.0264

Gnomad4 NFE AF: 0.0401

Gnomad4 OTH AF: 0.0474

Alfa AF: 0.0418 Hom.: 31

Bravo AF: 0.0386

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 18, 2014	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 28, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.41
DANN	Benign	0.27

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

Publications

LitVar

Other links and lift over

dbSNP: rs41304383; hg19: chr15-28116282;