rs145242923
Positions:
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
ENST00000354638.8 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.304
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 |
---|---|---|---|---|---|---|---|---|
OCA2 | NM_000275.3 | c.574-19A>G | intron_variant | ENST00000354638.8 | NP_000266.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OCA2 | ENST00000354638.8 | c.574-19A>G | intron_variant | 1 | NM_000275.3 | ENSP00000346659 | P1 | |||
OCA2 | ENST00000353809.9 | c.574-19A>G | intron_variant | 1 | ENSP00000261276 | |||||
OCA2 | ENST00000431101.1 | c.574-19A>G | intron_variant | 3 | ENSP00000415431 | |||||
OCA2 | ENST00000445578.5 | c.573+2253A>G | intron_variant | 3 | ENSP00000414425 |
Frequencies
GnomAD3 genomes AF: 0.00632 AC: 962AN: 152182Hom.: 6 Cov.: 33
GnomAD3 genomes
AF:
AC:
962
AN:
152182
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00652 AC: 1635AN: 250850Hom.: 10 AF XY: 0.00698 AC XY: 947AN XY: 135666
GnomAD3 exomes
AF:
AC:
1635
AN:
250850
Hom.:
AF XY:
AC XY:
947
AN XY:
135666
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00894 AC: 12882AN: 1441292Hom.: 73 Cov.: 28 AF XY: 0.00888 AC XY: 6377AN XY: 718466
GnomAD4 exome
AF:
AC:
12882
AN:
1441292
Hom.:
Cov.:
28
AF XY:
AC XY:
6377
AN XY:
718466
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00632 AC: 962AN: 152300Hom.: 7 Cov.: 33 AF XY: 0.00599 AC XY: 446AN XY: 74476
GnomAD4 genome
AF:
AC:
962
AN:
152300
Hom.:
Cov.:
33
AF XY:
AC XY:
446
AN XY:
74476
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
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 submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2022 | OCA2: BS2 - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 27, 2017 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Disclaimer: 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 provided | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 15, 2023 | This 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 submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at