rs1800413

Variant names:

• chr15-27957597-G-A
• rs1800413
• NM_000275.3:c.1775C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000275.3(OCA2):​c.1775C>T​(p.Thr592Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: OCA2 NM_000275.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.26
• 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: ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.933

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.1775C>T	p.Thr592Ile	missense	Exon 16 of 24	NP_000266.2	Q04671-1
	OCA2	NM_001300984.2		c.1703C>T	p.Thr568Ile	missense	Exon 15 of 23	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.1775C>T	p.Thr592Ile	missense	Exon 16 of 24	ENSP00000346659.3	Q04671-1
	OCA2	ENST00000353809.9	TSL:1	c.1703C>T	p.Thr568Ile	missense	Exon 15 of 23	ENSP00000261276.8	Q04671-2
	OCA2	ENST00000910120.1		c.1775C>T	p.Thr592Ile	missense	Exon 16 of 26	ENSP00000580179.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.86	D
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.037
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.032	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	0.27	D
MutationAssessor	Benign	1.9	L
PhyloP100		4.3
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.6	D
REVEL	Pathogenic	0.70
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.017	D
Polyphen		0.10	B
Vest4		0.72
MutPred		0.85		Loss of disorder (P = 0.0806)
MVP		0.98
MPC		0.47
ClinPred		0.98	D
GERP RS		2.5
Varity_R		0.40
gMVP		0.66
Mutation Taster		=3/97	disease causing

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: rs1800413; hg19: chr15-28202743;