rs17566952

Variant names:

• chr15-27951739-C-G
• rs17566952
• NM_000275.3:c.1951+45G>C

Your query was ambiguous. Multiple possible variants found:

• chr15-27951739-C-G
• chr15-27951739-C-T

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.1951+45G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0619 in 1,346,208 control chromosomes in the GnomAD database, including 3,369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.048 (255 hom., cov: 33)
  • Exomes 𝑓: 0.064 (3114 hom.)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.619
• Publications: 5 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=-0.82).
• BP6: Variant 15-27951739-C-G is Benign according to our data. Variant chr15-27951739-C-G is described in ClinVar as Benign. ClinVar VariationId is 1262515.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.122 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	NM_000275.3	MANE Select	c.1951+45G>C		intron	N/A	NP_000266.2
	OCA2	NM_001300984.2		c.1879+45G>C		intron	N/A	NP_001287913.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	ENST00000354638.8	TSL:1 MANE Select	c.1951+45G>C		intron	N/A	ENSP00000346659.3
	OCA2	ENST00000353809.9	TSL:1	c.1879+45G>C		intron	N/A	ENSP00000261276.8

Frequencies

GnomAD3 genomes AF: 0.0479 AC: 7287 AN: 152176 Hom.: 254 Cov.: 33

Gnomad AFR AF: 0.0114

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.0650

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.00751

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0264

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0604

Gnomad OTH AF: 0.0650

GnomAD2 exomes AF: 0.0599 AC: 14348 AN: 239646 AF XY: 0.0661

Gnomad AFR exome AF: 0.00999

Gnomad AMR exome AF: 0.0357

Gnomad ASJ exome AF: 0.154

Gnomad EAS exome AF: 0.00626

Gnomad FIN exome AF: 0.0315

Gnomad NFE exome AF: 0.0623

Gnomad OTH exome AF: 0.0710

GnomAD4 exome AF: 0.0637 AC: 76007 AN: 1193914 Hom.: 3114 Cov.: 16 AF XY: 0.0665 AC XY: 40363 AN XY: 606538

African (AFR) AF: 0.00903 AC: 252 AN: 27904

American (AMR) AF: 0.0380 AC: 1663 AN: 43778

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 3705 AN: 24426

East Asian (EAS) AF: 0.00455 AC: 173 AN: 38022

South Asian (SAS) AF: 0.129 AC: 10224 AN: 79398

European-Finnish (FIN) AF: 0.0308 AC: 1631 AN: 52896

Middle Eastern (MID) AF: 0.124 AC: 651 AN: 5240

European-Non Finnish (NFE) AF: 0.0623 AC: 54240 AN: 870878

Other (OTH) AF: 0.0675 AC: 3468 AN: 51372

GnomAD4 genome AF: 0.0478 AC: 7284 AN: 152294 Hom.: 255 Cov.: 33 AF XY: 0.0491 AC XY: 3656 AN XY: 74454

African (AFR) AF: 0.0114 AC: 474 AN: 41570

American (AMR) AF: 0.0649 AC: 992 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 490 AN: 3470

East Asian (EAS) AF: 0.00753 AC: 39 AN: 5180

South Asian (SAS) AF: 0.130 AC: 628 AN: 4828

European-Finnish (FIN) AF: 0.0264 AC: 280 AN: 10622

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0604 AC: 4105 AN: 68010

Other (OTH) AF: 0.0643 AC: 136 AN: 2114

Alfa AF: 0.0440 Hom.: 63

Bravo AF: 0.0466

Asia WGS AF: 0.0500 AC: 172 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jun 20, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.37
DANN	Benign	0.55
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17566952; hg19: chr15-28196885; COSMIC: COSV62347680;