15-27954159-A-C

Variant names:

• chr15-27954159-A-C
• rs4778211
• NM_000275.3:c.1842+999T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000275.3(OCA2):​c.1842+999T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.031 (40 hom., cov: 0)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0309 (1703/55060) while in subpopulation AFR AF = 0.0468 (1309/28000). AF 95% confidence interval is 0.0446. There are 40 homozygotes in GnomAd4. There are 834 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 40 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	NM_000275.3	MANE Select	c.1842+999T>G		intron	N/A	NP_000266.2
	OCA2	NM_001300984.2		c.1770+999T>G		intron	N/A	NP_001287913.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	ENST00000354638.8	TSL:1 MANE Select	c.1842+999T>G		intron	N/A	ENSP00000346659.3
	OCA2	ENST00000353809.9	TSL:1	c.1770+999T>G		intron	N/A	ENSP00000261276.8
	OCA2	ENST00000910120.1		c.1842+999T>G		intron	N/A	ENSP00000580179.1

Frequencies

GnomAD3 genomes AF: 0.0309 AC: 1696 AN: 54942 Hom.: 40 Cov.: 0

Gnomad AFR AF: 0.0467

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0214

Gnomad ASJ AF: 0.00648

Gnomad EAS AF: 0.0137

Gnomad SAS AF: 0.0149

Gnomad FIN AF: 0.00341

Gnomad MID AF: 0.0227

Gnomad NFE AF: 0.0135

Gnomad OTH AF: 0.0179

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0309 AC: 1703 AN: 55060 Hom.: 40 Cov.: 0 AF XY: 0.0309 AC XY: 834 AN XY: 27000

African (AFR) AF: 0.0467 AC: 1309 AN: 28000

American (AMR) AF: 0.0213 AC: 129 AN: 6044

Ashkenazi Jewish (ASJ) AF: 0.00648 AC: 5 AN: 772

East Asian (EAS) AF: 0.0138 AC: 65 AN: 4720

South Asian (SAS) AF: 0.0149 AC: 29 AN: 1952

European-Finnish (FIN) AF: 0.00341 AC: 7 AN: 2052

Middle Eastern (MID) AF: 0.0227 AC: 1 AN: 44

European-Non Finnish (NFE) AF: 0.0135 AC: 145 AN: 10708

Other (OTH) AF: 0.0175 AC: 13 AN: 744

Alfa AF: 0.808 Hom.: 70949

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.62
DANN	Benign	0.39
PhyloP100		-1.9
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: rs4778211; hg19: chr15-28199305; COSMIC: COSV62349879;