15-28099092-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000275.3(OCA2):​c.-22+132T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 155,530 control chromosomes in the GnomAD database, including 2,284 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 0.13 ( 2198 hom., cov: 33)
Exomes 𝑓: 0.13 ( 86 hom. )

Consequence

OCA2
NM_000275.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0940
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OCA2NM_000275.3 linkuse as main transcriptc.-22+132T>C intron_variant ENST00000354638.8 NP_000266.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OCA2ENST00000354638.8 linkuse as main transcriptc.-22+132T>C intron_variant 1 NM_000275.3 ENSP00000346659 P1Q04671-1
OCA2ENST00000353809.9 linkuse as main transcriptc.-22+132T>C intron_variant 1 ENSP00000261276 Q04671-2
OCA2ENST00000431101.1 linkuse as main transcriptc.-22+19T>C intron_variant 3 ENSP00000415431
OCA2ENST00000445578.5 linkuse as main transcriptc.-22+132T>C intron_variant 3 ENSP00000414425

Frequencies

GnomAD3 genomes
AF:
0.127
AC:
19234
AN:
152042
Hom.:
2200
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.153
Gnomad AMI
AF:
0.307
Gnomad AMR
AF:
0.166
Gnomad ASJ
AF:
0.123
Gnomad EAS
AF:
0.656
Gnomad SAS
AF:
0.242
Gnomad FIN
AF:
0.0179
Gnomad MID
AF:
0.250
Gnomad NFE
AF:
0.0667
Gnomad OTH
AF:
0.154
GnomAD4 exome
AF:
0.134
AC:
453
AN:
3370
Hom.:
86
Cov.:
0
AF XY:
0.129
AC XY:
238
AN XY:
1838
show subpopulations
Gnomad4 AFR exome
AF:
0.179
Gnomad4 AMR exome
AF:
0.125
Gnomad4 ASJ exome
AF:
0.0714
Gnomad4 EAS exome
AF:
0.627
Gnomad4 SAS exome
AF:
0.313
Gnomad4 FIN exome
AF:
0.0231
Gnomad4 NFE exome
AF:
0.0812
Gnomad4 OTH exome
AF:
0.0915
GnomAD4 genome
AF:
0.127
AC:
19253
AN:
152160
Hom.:
2198
Cov.:
33
AF XY:
0.132
AC XY:
9821
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.153
Gnomad4 AMR
AF:
0.166
Gnomad4 ASJ
AF:
0.123
Gnomad4 EAS
AF:
0.656
Gnomad4 SAS
AF:
0.241
Gnomad4 FIN
AF:
0.0179
Gnomad4 NFE
AF:
0.0667
Gnomad4 OTH
AF:
0.152
Alfa
AF:
0.0956
Hom.:
1654
Bravo
AF:
0.142
Asia WGS
AF:
0.365
AC:
1266
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
5.1
DANN
Benign
0.54

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs7495174; hg19: chr15-28344238; API