rs1800411

Variant names:

• chr15-27966775-G-A
• rs1800411
• NM_000275.3:c.1551C>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.1551C>T​(p.Cys517Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 1,612,640 control chromosomes in the GnomAD database, including 352,262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (25293 hom., cov: 32)
  • Exomes 𝑓: 0.65 (326969 hom.)
• Consequence: OCA2 NM_000275.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 2.05
• 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=-0.47).
• BP6: Variant 15-27966775-G-A is Benign according to our data. Variant chr15-27966775-G-A is described in ClinVar as Benign. ClinVar VariationId is 255722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.711 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.1551C>T	p.Cys517Cys	synonymous	Exon 15 of 24	NP_000266.2	Q04671-1
	OCA2	NM_001300984.2		c.1479C>T	p.Cys493Cys	synonymous	Exon 14 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.1551C>T	p.Cys517Cys	synonymous	Exon 15 of 24	ENSP00000346659.3	Q04671-1
	OCA2	ENST00000353809.9	TSL:1	c.1479C>T	p.Cys493Cys	synonymous	Exon 14 of 23	ENSP00000261276.8	Q04671-2
	OCA2	ENST00000910120.1		c.1551C>T	p.Cys517Cys	synonymous	Exon 15 of 26	ENSP00000580179.1

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81461 AN: 151866 Hom.: 25301 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.532

GnomAD2 exomes AF: 0.555 AC: 139169 AN: 250936 AF XY: 0.559

Gnomad AFR exome AF: 0.274

Gnomad AMR exome AF: 0.382

Gnomad ASJ exome AF: 0.595

Gnomad EAS exome AF: 0.147

Gnomad FIN exome AF: 0.743

Gnomad NFE exome AF: 0.718

Gnomad OTH exome AF: 0.605

GnomAD4 exome AF: 0.652 AC: 952314 AN: 1460656 Hom.: 326969 Cov.: 43 AF XY: 0.646 AC XY: 469183 AN XY: 726640

African (AFR) AF: 0.260 AC: 8699 AN: 33456

American (AMR) AF: 0.392 AC: 17538 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 15605 AN: 26130

East Asian (EAS) AF: 0.118 AC: 4677 AN: 39700

South Asian (SAS) AF: 0.386 AC: 33314 AN: 86202

European-Finnish (FIN) AF: 0.744 AC: 39708 AN: 53406

Middle Eastern (MID) AF: 0.592 AC: 3090 AN: 5222

European-Non Finnish (NFE) AF: 0.713 AC: 793043 AN: 1111530

Other (OTH) AF: 0.608 AC: 36640 AN: 60308

GnomAD4 genome AF: 0.536 AC: 81464 AN: 151984 Hom.: 25293 Cov.: 32 AF XY: 0.531 AC XY: 39436 AN XY: 74288

African (AFR) AF: 0.280 AC: 11606 AN: 41418

American (AMR) AF: 0.440 AC: 6715 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2066 AN: 3468

East Asian (EAS) AF: 0.150 AC: 775 AN: 5160

South Asian (SAS) AF: 0.368 AC: 1768 AN: 4810

European-Finnish (FIN) AF: 0.744 AC: 7861 AN: 10572

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.716 AC: 48694 AN: 67970

Other (OTH) AF: 0.529 AC: 1117 AN: 2112

Alfa AF: 0.616 Hom.: 32399

Bravo AF: 0.505

Asia WGS AF: 0.309 AC: 1076 AN: 3478

EpiCase AF: 0.692

EpiControl AF: 0.685

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	not provided (2)
-	-	2	Tyrosinase-positive oculocutaneous albinism (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	6.6
DANN	Benign	0.46
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs1800411; hg19: chr15-28211921; COSMIC: COSV62347205;