NM_000275.3:c.2432+31197T>C

Variant names:

• chr15-27813762-A-G
• rs1498521
• NM_000275.3:c.2432+31197T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000275.3(OCA2):​c.2432+31197T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 152,008 control chromosomes in the GnomAD database, including 26,883 homozygotes. 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 0.59 (26883 hom., cov: 32)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 3 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.747 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	NM_000275.3	MANE Select	c.2432+31197T>C		intron	N/A	NP_000266.2
	OCA2	NM_001300984.2		c.2360+31197T>C		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.2432+31197T>C		intron	N/A	ENSP00000346659.3
	OCA2	ENST00000353809.9	TSL:1	c.2360+31197T>C		intron	N/A	ENSP00000261276.8

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89640 AN: 151890 Hom.: 26882 Cov.: 32

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.662

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

GnomAD4 genome AF: 0.590 AC: 89685 AN: 152008 Hom.: 26883 Cov.: 32 AF XY: 0.589 AC XY: 43767 AN XY: 74304

African (AFR) AF: 0.616 AC: 25543 AN: 41454

American (AMR) AF: 0.629 AC: 9610 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2303 AN: 3472

East Asian (EAS) AF: 0.459 AC: 2354 AN: 5132

South Asian (SAS) AF: 0.768 AC: 3695 AN: 4814

European-Finnish (FIN) AF: 0.446 AC: 4718 AN: 10580

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39283 AN: 67972

Other (OTH) AF: 0.660 AC: 1390 AN: 2106

Alfa AF: 0.589 Hom.: 20269

Bravo AF: 0.599

Asia WGS AF: 0.613 AC: 2132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.33
DANN	Benign	0.62
PhyloP100		-1.1
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: rs1498521; hg19: chr15-28058908;