rs1800410

Variant names:

• chr15-27985038-T-C
• rs1800410
• NM_000275.3:c.1364+26A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-27985038-T-C
• chr15-27985038-T-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000275.3(OCA2):​c.1364+26A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,612,654 control chromosomes in the GnomAD database, including 37,406 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (5112 hom., cov: 33)
  • Exomes 𝑓: 0.16 (32294 hom.)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.80
• Publications: 12 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-27985038-T-C is Benign according to our data. Variant chr15-27985038-T-C is described in ClinVar as Benign. ClinVar VariationId is 1273632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.827 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.1364+26A>G		intron	N/A	NP_000266.2	Q04671-1
	OCA2	NM_001300984.2		c.1292+26A>G		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.1364+26A>G		intron	N/A	ENSP00000346659.3	Q04671-1
	OCA2	ENST00000353809.9	TSL:1	c.1292+26A>G		intron	N/A	ENSP00000261276.8	Q04671-2
	OCA2	ENST00000910120.1		c.1364+26A>G		intron	N/A	ENSP00000580179.1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32386 AN: 151976 Hom.: 5109 Cov.: 33

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.219

GnomAD2 exomes AF: 0.237 AC: 58637 AN: 247242 AF XY: 0.229

Gnomad AFR exome AF: 0.290

Gnomad AMR exome AF: 0.348

Gnomad ASJ exome AF: 0.212

Gnomad EAS exome AF: 0.848

Gnomad FIN exome AF: 0.130

Gnomad NFE exome AF: 0.119

Gnomad OTH exome AF: 0.196

GnomAD4 exome AF: 0.160 AC: 234024 AN: 1460560 Hom.: 32294 Cov.: 35 AF XY: 0.162 AC XY: 117472 AN XY: 726572

African (AFR) AF: 0.289 AC: 9670 AN: 33450

American (AMR) AF: 0.338 AC: 15024 AN: 44504

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 5481 AN: 26128

East Asian (EAS) AF: 0.880 AC: 34879 AN: 39614

South Asian (SAS) AF: 0.247 AC: 21314 AN: 86160

European-Finnish (FIN) AF: 0.128 AC: 6786 AN: 53166

Middle Eastern (MID) AF: 0.185 AC: 1065 AN: 5758

European-Non Finnish (NFE) AF: 0.116 AC: 128644 AN: 1111428

Other (OTH) AF: 0.185 AC: 11161 AN: 60352

GnomAD4 genome AF: 0.213 AC: 32434 AN: 152094 Hom.: 5112 Cov.: 33 AF XY: 0.219 AC XY: 16300 AN XY: 74340

African (AFR) AF: 0.290 AC: 12021 AN: 41492

American (AMR) AF: 0.270 AC: 4126 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 694 AN: 3470

East Asian (EAS) AF: 0.848 AC: 4355 AN: 5134

South Asian (SAS) AF: 0.265 AC: 1274 AN: 4814

European-Finnish (FIN) AF: 0.128 AC: 1359 AN: 10590

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7982 AN: 67990

Other (OTH) AF: 0.219 AC: 461 AN: 2106

Alfa AF: 0.156 Hom.: 1958

Bravo AF: 0.230

Asia WGS AF: 0.482 AC: 1670 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.046
DANN	Benign	0.31
PhyloP100		-2.8
Mutation Taster		=100/0	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: rs1800410; hg19: chr15-28230184;