NM_000275.3:c.228-9484G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000275.3(OCA2):​c.228-9484G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,048 control chromosomes in the GnomAD database, including 5,392 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 0.23 ( 5392 hom., cov: 33)

Consequence

OCA2
NM_000275.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0890

Publications

3 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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P, ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OCA2NM_000275.3 linkc.228-9484G>T intron_variant Intron 2 of 23 ENST00000354638.8 NP_000266.2 Q04671-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OCA2ENST00000354638.8 linkc.228-9484G>T intron_variant Intron 2 of 23 1 NM_000275.3 ENSP00000346659.3 Q04671-1
OCA2ENST00000353809.9 linkc.228-9484G>T intron_variant Intron 2 of 22 1 ENSP00000261276.8 Q04671-2
OCA2ENST00000431101.1 linkc.228-9484G>T intron_variant Intron 2 of 6 3 ENSP00000415431.1 C9JDV3
OCA2ENST00000445578.5 linkc.228-9484G>T intron_variant Intron 2 of 5 3 ENSP00000414425.1 C9JLG9

Frequencies

GnomAD3 genomes
AF:
0.225
AC:
34213
AN:
151930
Hom.:
5362
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.439
Gnomad AMI
AF:
0.121
Gnomad AMR
AF:
0.255
Gnomad ASJ
AF:
0.138
Gnomad EAS
AF:
0.222
Gnomad SAS
AF:
0.252
Gnomad FIN
AF:
0.123
Gnomad MID
AF:
0.294
Gnomad NFE
AF:
0.108
Gnomad OTH
AF:
0.243
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.226
AC:
34303
AN:
152048
Hom.:
5392
Cov.:
33
AF XY:
0.229
AC XY:
17058
AN XY:
74336
show subpopulations
African (AFR)
AF:
0.440
AC:
18211
AN:
41428
American (AMR)
AF:
0.255
AC:
3888
AN:
15270
Ashkenazi Jewish (ASJ)
AF:
0.138
AC:
478
AN:
3470
East Asian (EAS)
AF:
0.222
AC:
1150
AN:
5182
South Asian (SAS)
AF:
0.252
AC:
1213
AN:
4820
European-Finnish (FIN)
AF:
0.123
AC:
1306
AN:
10584
Middle Eastern (MID)
AF:
0.299
AC:
88
AN:
294
European-Non Finnish (NFE)
AF:
0.108
AC:
7332
AN:
67976
Other (OTH)
AF:
0.250
AC:
527
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1228
2456
3683
4911
6139
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
322
644
966
1288
1610
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.178
Hom.:
471
Bravo
AF:
0.242
Asia WGS
AF:
0.296
AC:
1027
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
4.3
DANN
Benign
0.49
PhyloP100
-0.089
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

Publications

Other links and lift over

dbSNP: rs12324648; hg19: chr15-28286793; API