rs145242923

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The ENST00000354638.8(OCA2):​c.574-19A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00869 in 1,593,592 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0063 ( 7 hom., cov: 33)
Exomes 𝑓: 0.0089 ( 73 hom. )

Consequence

OCA2
ENST00000354638.8 intron

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: -0.304
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
Variant 15-28022592-T-C is Benign according to our data. Variant chr15-28022592-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 504924.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1, Likely_benign=3}.
BS2
High Homozygotes in GnomAd4 at 7 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OCA2NM_000275.3 linkuse as main transcriptc.574-19A>G 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.574-19A>G intron_variant 1 NM_000275.3 ENSP00000346659 P1Q04671-1
OCA2ENST00000353809.9 linkuse as main transcriptc.574-19A>G intron_variant 1 ENSP00000261276 Q04671-2
OCA2ENST00000431101.1 linkuse as main transcriptc.574-19A>G intron_variant 3 ENSP00000415431
OCA2ENST00000445578.5 linkuse as main transcriptc.573+2253A>G intron_variant 3 ENSP00000414425

Frequencies

GnomAD3 genomes
AF:
0.00632
AC:
962
AN:
152182
Hom.:
6
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00237
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00877
Gnomad ASJ
AF:
0.0109
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00747
Gnomad FIN
AF:
0.00122
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00920
Gnomad OTH
AF:
0.00718
GnomAD3 exomes
AF:
0.00652
AC:
1635
AN:
250850
Hom.:
10
AF XY:
0.00698
AC XY:
947
AN XY:
135666
show subpopulations
Gnomad AFR exome
AF:
0.00204
Gnomad AMR exome
AF:
0.00637
Gnomad ASJ exome
AF:
0.0130
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00645
Gnomad FIN exome
AF:
0.00167
Gnomad NFE exome
AF:
0.00849
Gnomad OTH exome
AF:
0.00884
GnomAD4 exome
AF:
0.00894
AC:
12882
AN:
1441292
Hom.:
73
Cov.:
28
AF XY:
0.00888
AC XY:
6377
AN XY:
718466
show subpopulations
Gnomad4 AFR exome
AF:
0.00154
Gnomad4 AMR exome
AF:
0.00680
Gnomad4 ASJ exome
AF:
0.0109
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.00660
Gnomad4 FIN exome
AF:
0.00137
Gnomad4 NFE exome
AF:
0.0101
Gnomad4 OTH exome
AF:
0.00789
GnomAD4 genome
AF:
0.00632
AC:
962
AN:
152300
Hom.:
7
Cov.:
33
AF XY:
0.00599
AC XY:
446
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.00236
Gnomad4 AMR
AF:
0.00876
Gnomad4 ASJ
AF:
0.0109
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00768
Gnomad4 FIN
AF:
0.00122
Gnomad4 NFE
AF:
0.00919
Gnomad4 OTH
AF:
0.00710
Alfa
AF:
0.00867
Hom.:
4
Bravo
AF:
0.00642
Asia WGS
AF:
0.00115
AC:
4
AN:
3478

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:5
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Uncertain:1Benign:2
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJul 01, 2022OCA2: BS2 -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
Uncertain significance, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Oct 27, 2017- -
not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 28, 2016Disclaimer: This variant has not undergone full assessment. The following are pr eliminary notes: outside ROI. OB 12/14/15: One compound het patient with with oc ular albinism who had exon 7 deletion and this variant was reported (Spritz 1995 ). Freq 1.1% -
OCA2-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesMar 15, 2023This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Tyrosinase-positive oculocutaneous albinism Benign:1
Likely benign, criteria provided, single submitterclinical testingGenome-Nilou LabNov 07, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
CADD
Benign
0.13
DANN
Benign
0.35

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
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: rs145242923; hg19: chr15-28267738; API