rs7173419

Variant names:

• chr15-27951675-T-C
• rs7173419
• NM_000275.3:c.1951+109A>G

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.1951+109A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 821,232 control chromosomes in the GnomAD database, including 195,446 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (30259 hom., cov: 32)
  • Exomes 𝑓: 0.68 (165187 hom.)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0710
• Publications: 13 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=-0.99).
• BP6: Variant 15-27951675-T-C is Benign according to our data. Variant chr15-27951675-T-C is described in ClinVar as Benign. ClinVar VariationId is 1239793.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.77 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.1951+109A>G		intron	N/A	NP_000266.2	Q04671-1
	OCA2	NM_001300984.2		c.1879+109A>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.1951+109A>G		intron	N/A	ENSP00000346659.3	Q04671-1
	OCA2	ENST00000353809.9	TSL:1	c.1879+109A>G		intron	N/A	ENSP00000261276.8	Q04671-2
	OCA2	ENST00000910120.1		c.1951+109A>G		intron	N/A	ENSP00000580179.1

Frequencies

GnomAD3 genomes AF: 0.594 AC: 90270 AN: 151932 Hom.: 30267 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.866

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.601

GnomAD4 exome AF: 0.677 AC: 453223 AN: 669182 Hom.: 165187 AF XY: 0.672 AC XY: 239468 AN XY: 356438

African (AFR) AF: 0.338 AC: 5931 AN: 17522

American (AMR) AF: 0.433 AC: 15329 AN: 35400

Ashkenazi Jewish (ASJ) AF: 0.743 AC: 15380 AN: 20700

East Asian (EAS) AF: 0.0978 AC: 3190 AN: 32602

South Asian (SAS) AF: 0.493 AC: 31969 AN: 64834

European-Finnish (FIN) AF: 0.764 AC: 35216 AN: 46086

Middle Eastern (MID) AF: 0.700 AC: 3004 AN: 4290

European-Non Finnish (NFE) AF: 0.775 AC: 320434 AN: 413396

Other (OTH) AF: 0.663 AC: 22770 AN: 34352

GnomAD4 genome AF: 0.594 AC: 90287 AN: 152050 Hom.: 30259 Cov.: 32 AF XY: 0.588 AC XY: 43720 AN XY: 74316

African (AFR) AF: 0.342 AC: 14169 AN: 41442

American (AMR) AF: 0.501 AC: 7649 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.731 AC: 2536 AN: 3468

East Asian (EAS) AF: 0.136 AC: 701 AN: 5148

South Asian (SAS) AF: 0.470 AC: 2266 AN: 4818

European-Finnish (FIN) AF: 0.751 AC: 7959 AN: 10594

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.776 AC: 52747 AN: 67982

Other (OTH) AF: 0.598 AC: 1262 AN: 2112

Alfa AF: 0.692 Hom.: 7284

Bravo AF: 0.564

Asia WGS AF: 0.338 AC: 1178 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	-0.99
CADD	Benign	6.2
DANN	Benign	0.63
PhyloP100		0.071
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: rs7173419; hg19: chr15-28196821; COSMIC: COSV62347676;