15-27957495-C-T

Variant names:

• chr15-27957495-C-T
• rs45495598
• NM_000275.3:c.1784+93G>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.1784+93G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0599 in 1,409,974 control chromosomes in the GnomAD database, including 3,286 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.046 (247 hom., cov: 33)
  • Exomes 𝑓: 0.061 (3039 hom.)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0670
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 15-27957495-C-T is Benign according to our data. Variant chr15-27957495-C-T is described in ClinVar as Benign. ClinVar VariationId is 1226185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.12 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.1784+93G>A		intron	N/A	NP_000266.2
	OCA2	NM_001300984.2		c.1712+93G>A		intron	N/A	NP_001287913.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	ENST00000354638.8	TSL:1 MANE Select	c.1784+93G>A		intron	N/A	ENSP00000346659.3
	OCA2	ENST00000353809.9	TSL:1	c.1712+93G>A		intron	N/A	ENSP00000261276.8
	OCA2	ENST00000910120.1		c.1784+93G>A		intron	N/A	ENSP00000580179.1

Frequencies

GnomAD3 genomes AF: 0.0464 AC: 7060 AN: 152152 Hom.: 247 Cov.: 33

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.0624

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.00771

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0271

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.0581

Gnomad OTH AF: 0.0660

GnomAD4 exome AF: 0.0615 AC: 77341 AN: 1257704 Hom.: 3039 AF XY: 0.0644 AC XY: 40810 AN XY: 633790

African (AFR) AF: 0.00878 AC: 260 AN: 29596

American (AMR) AF: 0.0373 AC: 1653 AN: 44304

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 3752 AN: 24790

East Asian (EAS) AF: 0.00471 AC: 182 AN: 38618

South Asian (SAS) AF: 0.127 AC: 10453 AN: 82006

European-Finnish (FIN) AF: 0.0316 AC: 1558 AN: 49310

Middle Eastern (MID) AF: 0.124 AC: 472 AN: 3802

European-Non Finnish (NFE) AF: 0.0595 AC: 55479 AN: 931678

Other (OTH) AF: 0.0659 AC: 3532 AN: 53600

GnomAD4 genome AF: 0.0463 AC: 7056 AN: 152270 Hom.: 247 Cov.: 33 AF XY: 0.0476 AC XY: 3545 AN XY: 74470

African (AFR) AF: 0.0104 AC: 431 AN: 41566

American (AMR) AF: 0.0623 AC: 953 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 491 AN: 3466

East Asian (EAS) AF: 0.00773 AC: 40 AN: 5174

South Asian (SAS) AF: 0.129 AC: 620 AN: 4822

European-Finnish (FIN) AF: 0.0271 AC: 288 AN: 10614

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.0581 AC: 3954 AN: 68014

Other (OTH) AF: 0.0653 AC: 138 AN: 2112

Alfa AF: 0.0483 Hom.: 37

Bravo AF: 0.0452

Asia WGS AF: 0.0500 AC: 173 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.88
CADD	Benign	1.1
DANN	Benign	0.47
PhyloP100		-0.067
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: rs45495598; hg19: chr15-28202641; COSMIC: COSV107418659;