rs759396151

Variant names:

• chr15-27755404-A-G
• rs759396151
• NM_000275.3:c.2501T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-27755404-A-G
• chr15-27755404-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000275.3(OCA2):​c.2501T>C​(p.Val834Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V834M) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OCA2 NM_000275.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.04

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25192598).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.2501T>C	p.Val834Ala	missense_variant	Exon 24 of 24	ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.2501T>C	p.Val834Ala	missense_variant	Exon 24 of 24	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.2429T>C	p.Val810Ala	missense_variant	Exon 23 of 23	1		ENSP00000261276.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.32	.;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.25	T;T
MetaSVM	Uncertain	0.043	D
MutationAssessor	Benign	0.30	.;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.6	N;N
REVEL	Uncertain	0.36
Sift	Benign	0.065	T;T
Sift4G	Benign	0.20	T;T
Polyphen		0.36	B;B
Vest4		0.16
MutPred		0.40		.;Gain of disorder (P = 0.0534);
MVP		0.95
MPC		0.16
ClinPred		0.46	T
GERP RS		5.8
Varity_R		0.11
gMVP		0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs759396151; hg19: chr15-28000550;