rs1900758

Variant names:

• chr15-27984951-C-T
• rs1900758
• NM_000275.3:c.1364+113G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-27984951-C-T
• chr15-27984951-C-A

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.1364+113G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 1,282,724 control chromosomes in the GnomAD database, including 261,509 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (22736 hom., cov: 33)
  • Exomes 𝑓: 0.62 (238773 hom.)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0900
• Publications: 10 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 15-27984951-C-T is Benign according to our data. Variant chr15-27984951-C-T is described in ClinVar as Benign. ClinVar VariationId is 1233186.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.698 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.1364+113G>A		intron	N/A	NP_000266.2	Q04671-1
	OCA2	NM_001300984.2		c.1292+113G>A		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.1364+113G>A		intron	N/A	ENSP00000346659.3	Q04671-1
	OCA2	ENST00000353809.9	TSL:1	c.1292+113G>A		intron	N/A	ENSP00000261276.8	Q04671-2
	OCA2	ENST00000910120.1		c.1364+113G>A		intron	N/A	ENSP00000580179.1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73997 AN: 152008 Hom.: 22742 Cov.: 33

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.0348

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.492

GnomAD4 exome AF: 0.624 AC: 705134 AN: 1130598 Hom.: 238773 AF XY: 0.615 AC XY: 352097 AN XY: 572276

African (AFR) AF: 0.171 AC: 4541 AN: 26538

American (AMR) AF: 0.302 AC: 10990 AN: 36372

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 13569 AN: 23550

East Asian (EAS) AF: 0.0209 AC: 727 AN: 34846

South Asian (SAS) AF: 0.314 AC: 23637 AN: 75238

European-Finnish (FIN) AF: 0.708 AC: 31956 AN: 45126

Middle Eastern (MID) AF: 0.590 AC: 2585 AN: 4384

European-Non Finnish (NFE) AF: 0.705 AC: 588874 AN: 835170

Other (OTH) AF: 0.572 AC: 28255 AN: 49374

GnomAD4 genome AF: 0.486 AC: 73975 AN: 152126 Hom.: 22736 Cov.: 33 AF XY: 0.479 AC XY: 35590 AN XY: 74368

African (AFR) AF: 0.180 AC: 7484 AN: 41500

American (AMR) AF: 0.380 AC: 5802 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2012 AN: 3472

East Asian (EAS) AF: 0.0348 AC: 180 AN: 5166

South Asian (SAS) AF: 0.285 AC: 1372 AN: 4822

European-Finnish (FIN) AF: 0.700 AC: 7419 AN: 10600

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.704 AC: 47821 AN: 67966

Other (OTH) AF: 0.487 AC: 1030 AN: 2114

Alfa AF: 0.609 Hom.: 5948

Bravo AF: 0.452

Asia WGS AF: 0.184 AC: 645 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.63
PhyloP100		-0.090
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: rs1900758; hg19: chr15-28230097; COSMIC: COSV62344991;