rs1800404

Variant names:

• chr15-27990627-C-T
• rs1800404
• NM_000275.3:c.1065G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-27990627-C-T
• chr15-27990627-C-A

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.1065G>A​(p.Ala355Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 1,613,344 control chromosomes in the GnomAD database, including 438,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (31157 hom., cov: 33)
  • Exomes 𝑓: 0.73 (407137 hom.)
• Consequence: OCA2 NM_000275.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.25
• Publications: 70 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=-0.52).
• BP6: Variant 15-27990627-C-T is Benign according to our data. Variant chr15-27990627-C-T is described in ClinVar as Benign. ClinVar VariationId is 255716.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.25 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.789 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.1065G>A	p.Ala355Ala	synonymous	Exon 10 of 24	NP_000266.2	Q04671-1
	OCA2	NM_001300984.2		c.1045-961G>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.1065G>A	p.Ala355Ala	synonymous	Exon 10 of 24	ENSP00000346659.3	Q04671-1
	OCA2	ENST00000353809.9	TSL:1	c.1045-961G>A		intron	N/A	ENSP00000261276.8	Q04671-2
	OCA2	ENST00000910120.1		c.1065G>A	p.Ala355Ala	synonymous	Exon 10 of 26	ENSP00000580179.1

Frequencies

GnomAD3 genomes AF: 0.586 AC: 89073 AN: 151998 Hom.: 31163 Cov.: 33

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.839

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.794

Gnomad OTH AF: 0.629

GnomAD2 exomes AF: 0.639 AC: 160311 AN: 251022 AF XY: 0.640

Gnomad AFR exome AF: 0.203

Gnomad AMR exome AF: 0.536

Gnomad ASJ exome AF: 0.706

Gnomad EAS exome AF: 0.382

Gnomad FIN exome AF: 0.829

Gnomad NFE exome AF: 0.798

Gnomad OTH exome AF: 0.701

GnomAD4 exome AF: 0.731 AC: 1068472 AN: 1461228 Hom.: 407137 Cov.: 48 AF XY: 0.723 AC XY: 525916 AN XY: 726944

African (AFR) AF: 0.191 AC: 6404 AN: 33470

American (AMR) AF: 0.542 AC: 24241 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.706 AC: 18449 AN: 26130

East Asian (EAS) AF: 0.403 AC: 15982 AN: 39690

South Asian (SAS) AF: 0.392 AC: 33804 AN: 86234

European-Finnish (FIN) AF: 0.830 AC: 44179 AN: 53246

Middle Eastern (MID) AF: 0.671 AC: 3870 AN: 5768

European-Non Finnish (NFE) AF: 0.791 AC: 879785 AN: 1111600

Other (OTH) AF: 0.692 AC: 41758 AN: 60372

GnomAD4 genome AF: 0.586 AC: 89067 AN: 152116 Hom.: 31157 Cov.: 33 AF XY: 0.583 AC XY: 43375 AN XY: 74388

African (AFR) AF: 0.215 AC: 8920 AN: 41486

American (AMR) AF: 0.570 AC: 8710 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2482 AN: 3470

East Asian (EAS) AF: 0.399 AC: 2052 AN: 5142

South Asian (SAS) AF: 0.363 AC: 1749 AN: 4818

European-Finnish (FIN) AF: 0.839 AC: 8892 AN: 10600

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.794 AC: 54016 AN: 68000

Other (OTH) AF: 0.624 AC: 1320 AN: 2116

Alfa AF: 0.708 Hom.: 63156

Bravo AF: 0.557

Asia WGS AF: 0.432 AC: 1506 AN: 3478

EpiCase AF: 0.783

EpiControl AF: 0.780

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)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.35
DANN	Benign	0.52
PhyloP100		-1.2
Mutation Taster		=91/9	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: rs1800404; hg19: chr15-28235773; COSMIC: COSV62338507;