GeneBe

rs74653330

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1PM2

The NM_000275.3(OCA2):​c.1441G>T​(p.Ala481Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. A481T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

OCA2
NM_000275.3 missense

Scores

1
11
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.40

Publications

0 publications found
Variant links:
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

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ACMG classification

Classification was made for transcript

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

PM1
In a hotspot region, there are 9 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 6 uncertain in NM_000275.3
PM2
Very rare variant in population databases, with high coverage;

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.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
OCA2
NM_000275.3
MANE Select
c.1441G>Tp.Ala481Ser
missense
Exon 14 of 24NP_000266.2Q04671-1
OCA2
NM_001300984.2
c.1369G>Tp.Ala457Ser
missense
Exon 13 of 23NP_001287913.1Q04671-2

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
OCA2
ENST00000354638.8
TSL:1 MANE Select
c.1441G>Tp.Ala481Ser
missense
Exon 14 of 24ENSP00000346659.3Q04671-1
OCA2
ENST00000353809.9
TSL:1
c.1369G>Tp.Ala457Ser
missense
Exon 13 of 23ENSP00000261276.8Q04671-2
OCA2
ENST00000910120.1
c.1441G>Tp.Ala481Ser
missense
Exon 14 of 26ENSP00000580179.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.020
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.60
D
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.94
D
M_CAP
Benign
0.055
D
MetaRNN
Uncertain
0.63
D
MetaSVM
Uncertain
0.10
D
MutationAssessor
Benign
2.0
M
PhyloP100
5.4
PrimateAI
Uncertain
0.70
T
PROVEAN
Benign
-1.9
N
REVEL
Uncertain
0.63
Sift
Benign
0.27
T
Sift4G
Benign
0.16
T
Polyphen
0.86
P
Vest4
0.59
MutPred
0.78
Gain of glycosylation at A481 (P = 0.0171)
MVP
0.86
MPC
0.39
ClinPred
0.97
D
GERP RS
5.1
Varity_R
0.29
gMVP
0.91

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

Other links and lift over

dbSNP: rs74653330; hg19: chr15-28228553; API