rs1800405

Variant names:

• chr15-27990579-G-A
• rs1800405
• NM_000275.3:c.1113C>T

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.1113C>T​(p.Gly371Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,613,562 control chromosomes in the GnomAD database, including 479 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (72 hom., cov: 32)
  • Exomes 𝑓: 0.014 (407 hom.)
• Consequence: OCA2 NM_000275.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -1.64
• Publications: 8 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=-0.9).
• BP6: Variant 15-27990579-G-A is Benign according to our data. Variant chr15-27990579-G-A is described in ClinVar as Benign. ClinVar VariationId is 193573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.64 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0809 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.1113C>T	p.Gly371Gly	synonymous	Exon 10 of 24	NP_000266.2	Q04671-1
	OCA2	NM_001300984.2		c.1045-913C>T		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.1113C>T	p.Gly371Gly	synonymous	Exon 10 of 24	ENSP00000346659.3	Q04671-1
	OCA2	ENST00000353809.9	TSL:1	c.1045-913C>T		intron	N/A	ENSP00000261276.8	Q04671-2
	OCA2	ENST00000910120.1		c.1113C>T	p.Gly371Gly	synonymous	Exon 10 of 26	ENSP00000580179.1

Frequencies

GnomAD3 genomes AF: 0.0165 AC: 2517 AN: 152126 Hom.: 71 Cov.: 32

Gnomad AFR AF: 0.00357

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0842

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0111

Gnomad OTH AF: 0.0220

GnomAD2 exomes AF: 0.0243 AC: 6102 AN: 251046 AF XY: 0.0218

Gnomad AFR exome AF: 0.00234

Gnomad AMR exome AF: 0.105

Gnomad ASJ exome AF: 0.00676

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0125

Gnomad NFE exome AF: 0.0107

Gnomad OTH exome AF: 0.0204

GnomAD4 exome AF: 0.0138 AC: 20138 AN: 1461318 Hom.: 407 Cov.: 30 AF XY: 0.0138 AC XY: 10024 AN XY: 726988

African (AFR) AF: 0.00218 AC: 73 AN: 33476

American (AMR) AF: 0.103 AC: 4609 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00742 AC: 194 AN: 26132

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39700

South Asian (SAS) AF: 0.0252 AC: 2177 AN: 86250

European-Finnish (FIN) AF: 0.0125 AC: 665 AN: 53224

Middle Eastern (MID) AF: 0.0121 AC: 70 AN: 5768

European-Non Finnish (NFE) AF: 0.0104 AC: 11521 AN: 1111668

Other (OTH) AF: 0.0136 AC: 821 AN: 60388

GnomAD4 genome AF: 0.0166 AC: 2525 AN: 152244 Hom.: 72 Cov.: 32 AF XY: 0.0181 AC XY: 1349 AN XY: 74440

African (AFR) AF: 0.00356 AC: 148 AN: 41538

American (AMR) AF: 0.0847 AC: 1296 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.0226 AC: 109 AN: 4826

European-Finnish (FIN) AF: 0.0136 AC: 144 AN: 10590

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0111 AC: 753 AN: 68024

Other (OTH) AF: 0.0217 AC: 46 AN: 2116

Alfa AF: 0.0102 Hom.: 9

Bravo AF: 0.0211

Asia WGS AF: 0.0120 AC: 43 AN: 3478

EpiCase AF: 0.00987

EpiControl AF: 0.0108

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	2	Tyrosinase-positive oculocutaneous albinism (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.45
DANN	Benign	0.27
PhyloP100		-1.6
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1800405; hg19: chr15-28235725; COSMIC: COSV62347626;