rs797044784
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5
The NM_000275.3(OCA2):c.819_822delinsGGTC(p.Asn273_Trp274delinsLysVal) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
OCA2
NM_000275.3 missense
NM_000275.3 missense
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.59
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 Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
PP5
?
Variant 15-28016172-CCAG-GACC is Pathogenic according to our data. Variant chr15-28016172-CCAG-GACC is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 198707.We mark this variant Likely_pathogenic, oryginal submissions are: {Pathogenic=6, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OCA2 | NM_000275.3 | c.819_822delinsGGTC | p.Asn273_Trp274delinsLysVal | missense_variant | 8/24 | ENST00000354638.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OCA2 | ENST00000354638.8 | c.819_822delinsGGTC | p.Asn273_Trp274delinsLysVal | missense_variant | 8/24 | 1 | NM_000275.3 | P1 | |
OCA2 | ENST00000353809.9 | c.819_822delinsGGTC | p.Asn273_Trp274delinsLysVal | missense_variant | 8/23 | 1 | |||
OCA2 | ENST00000445578.5 | c.585_588delinsGGTC | p.Asn195_Trp196delinsLysVal | missense_variant | 6/6 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:6Uncertain:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Pathogenic:2Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center | Dec 21, 2021 | PM2 - |
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 02, 2017 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jul 23, 2023 | In-frame deletion of 2 amino acids and insertion of 2 incorrect amino acids; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 15173252, 18821858, 12876664, 7874125, 28976636, 18680187, 33502802) - |
Tyrosinase-positive oculocutaneous albinism Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 13, 2017 | - - |
SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Feb 22, 2024 | - - |
OCA2-related disorder Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 20, 2022 | The OCA2 c.819_822delinsGGTC variant is predicted to result in an in-frame deletion and insertion. This variant has been reported to be causative for autosomal recessive oculocutaneous albinism (Garrison et al. 2004. PubMed ID: 15173252; King et al. 2003. PubMed ID: 12876664, reported as NW273KV; Lee. 1994. PubMed ID: 7874125, reported as N273K1W274V; Rooryck et al. 2008. PubMed ID: 18821858). At PreventionGenetics, we have observed this variant along with another pathogenic variant in several unrelated patients. This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Given the evidence, we interpret c.819_822delinsGGTC (p.Asn273_Trp274delinsLysVal) as pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at