rs1800419

Variant names:

• chr15-27851392-A-G
• rs1800419
• NM_000275.3:c.2328T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-27851392-A-G
• chr15-27851392-A-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000275.3(OCA2):​c.2328T>C​(p.Ala776Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 1,612,484 control chromosomes in the GnomAD database, including 152,875 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17884 hom., cov: 32)
  • Exomes 𝑓: 0.43 (134991 hom.)
• Consequence: OCA2 NM_000275.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 1.39
• Publications: 27 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 15-27851392-A-G is Benign according to our data. Variant chr15-27851392-A-G is described in ClinVar as Benign. ClinVar VariationId is 195643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.39 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.611 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.2328T>C	p.Ala776Ala	synonymous	Exon 22 of 24	NP_000266.2	Q04671-1
	OCA2	NM_001300984.2		c.2256T>C	p.Ala752Ala	synonymous	Exon 21 of 23	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.2328T>C	p.Ala776Ala	synonymous	Exon 22 of 24	ENSP00000346659.3	Q04671-1
	OCA2	ENST00000353809.9	TSL:1	c.2256T>C	p.Ala752Ala	synonymous	Exon 21 of 23	ENSP00000261276.8	Q04671-2
	OCA2	ENST00000910120.1		c.2574T>C	p.Ala858Ala	synonymous	Exon 24 of 26	ENSP00000580179.1

Frequencies

GnomAD3 genomes AF: 0.474 AC: 72097 AN: 151952 Hom.: 17866 Cov.: 32

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.533

GnomAD2 exomes AF: 0.435 AC: 107811 AN: 248098 AF XY: 0.439

Gnomad AFR exome AF: 0.623

Gnomad AMR exome AF: 0.365

Gnomad ASJ exome AF: 0.481

Gnomad EAS exome AF: 0.438

Gnomad FIN exome AF: 0.335

Gnomad NFE exome AF: 0.416

Gnomad OTH exome AF: 0.447

GnomAD4 exome AF: 0.425 AC: 621378 AN: 1460416 Hom.: 134991 Cov.: 39 AF XY: 0.429 AC XY: 311663 AN XY: 726484

African (AFR) AF: 0.629 AC: 21040 AN: 33464

American (AMR) AF: 0.373 AC: 16633 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 12607 AN: 26108

East Asian (EAS) AF: 0.417 AC: 16554 AN: 39660

South Asian (SAS) AF: 0.526 AC: 45281 AN: 86116

European-Finnish (FIN) AF: 0.334 AC: 17841 AN: 53360

Middle Eastern (MID) AF: 0.531 AC: 3049 AN: 5746

European-Non Finnish (NFE) AF: 0.415 AC: 461257 AN: 1110974

Other (OTH) AF: 0.449 AC: 27116 AN: 60342

GnomAD4 genome AF: 0.474 AC: 72148 AN: 152068 Hom.: 17884 Cov.: 32 AF XY: 0.471 AC XY: 35047 AN XY: 74332

African (AFR) AF: 0.617 AC: 25619 AN: 41498

American (AMR) AF: 0.427 AC: 6525 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1694 AN: 3468

East Asian (EAS) AF: 0.440 AC: 2260 AN: 5136

South Asian (SAS) AF: 0.537 AC: 2585 AN: 4818

European-Finnish (FIN) AF: 0.323 AC: 3415 AN: 10582

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.419 AC: 28498 AN: 67968

Other (OTH) AF: 0.536 AC: 1132 AN: 2112

Alfa AF: 0.449 Hom.: 11341

Bravo AF: 0.486

Asia WGS AF: 0.491 AC: 1708 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	2	Tyrosinase-positive oculocutaneous albinism (2)
-	-	1	Tyrosinase-positive oculocutaneous albinism;C1856895:SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	8.2
DANN	Benign	0.55
PhyloP100		1.4
Mutation Taster		=98/2	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: rs1800419; hg19: chr15-28096538; COSMIC: COSV62337410;