rs1800415

Variant names:

• chr15-27951848-C-A
• rs1800415
• NM_000275.3:c.1887G>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_000275.3(OCA2):​c.1887G>T​(p.Val629Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,614,058 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (28 hom., cov: 33)
  • Exomes 𝑓: 0.00097 (22 hom.)
• Consequence: OCA2 NM_000275.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.439
• Publications: 2 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 15-27951848-C-A is Benign according to our data. Variant chr15-27951848-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 255725.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.439 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0101 (1541/152300) while in subpopulation AFR AF = 0.0348 (1447/41560). AF 95% confidence interval is 0.0333. There are 28 homozygotes in GnomAd4. There are 727 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 28 AR gene

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.1887G>T	p.Val629Val	synonymous	Exon 18 of 24	NP_000266.2
	OCA2	NM_001300984.2		c.1815G>T	p.Val605Val	synonymous	Exon 17 of 23	NP_001287913.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	ENST00000354638.8	TSL:1 MANE Select	c.1887G>T	p.Val629Val	synonymous	Exon 18 of 24	ENSP00000346659.3
	OCA2	ENST00000353809.9	TSL:1	c.1815G>T	p.Val605Val	synonymous	Exon 17 of 23	ENSP00000261276.8
	OCA2	ENST00000910120.1		c.1887G>T	p.Val629Val	synonymous	Exon 18 of 26	ENSP00000580179.1

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1538 AN: 152182 Hom.: 28 Cov.: 33

Gnomad AFR AF: 0.0348

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00471

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00955

GnomAD2 exomes AF: 0.00270 AC: 680 AN: 251416 AF XY: 0.00206

Gnomad AFR exome AF: 0.0372

Gnomad AMR exome AF: 0.00182

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000651

GnomAD4 exome AF: 0.000966 AC: 1412 AN: 1461758 Hom.: 22 Cov.: 31 AF XY: 0.000799 AC XY: 581 AN XY: 727190

African (AFR) AF: 0.0347 AC: 1163 AN: 33468

American (AMR) AF: 0.00197 AC: 88 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111906

Other (OTH) AF: 0.00237 AC: 143 AN: 60392

GnomAD4 genome AF: 0.0101 AC: 1541 AN: 152300 Hom.: 28 Cov.: 33 AF XY: 0.00976 AC XY: 727 AN XY: 74470

African (AFR) AF: 0.0348 AC: 1447 AN: 41560

American (AMR) AF: 0.00471 AC: 72 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68030

Other (OTH) AF: 0.00945 AC: 20 AN: 2116

Alfa AF: 0.00503 Hom.: 13

Bravo AF: 0.0116

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Tyrosinase-positive oculocutaneous albinism (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	0.78
DANN	Benign	0.53
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1800415; hg19: chr15-28196994;