rs1800417
Positions:
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1
The NM_000275.3(OCA2):āc.2165T>Cā(p.Ile722Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00381 in 1,614,112 control chromosomes in the GnomAD database, including 118 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.016 ( 57 hom., cov: 33)
Exomes š: 0.0026 ( 61 hom. )
Consequence
OCA2
NM_000275.3 missense
NM_000275.3 missense
Scores
16
Clinical Significance
Conservation
PhyloP100: 5.15
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 -18 ACMG points.
PM1
?
In a transmembrane_region Helical (size 16) in uniprot entity P_HUMAN there are 7 pathogenic changes around while only 0 benign (100%) in NM_000275.3
BP4
?
Computational evidence support a benign effect (MetaRNN=0.006563753).
BP6
?
Variant 15-27871233-A-G is Benign according to our data. Variant chr15-27871233-A-G is described in ClinVar as [Benign]. Clinvar id is 255728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0517 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OCA2 | NM_000275.3 | c.2165T>C | p.Ile722Thr | missense_variant | 21/24 | ENST00000354638.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OCA2 | ENST00000354638.8 | c.2165T>C | p.Ile722Thr | missense_variant | 21/24 | 1 | NM_000275.3 | P1 | |
OCA2 | ENST00000353809.9 | c.2093T>C | p.Ile698Thr | missense_variant | 20/23 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0156 AC: 2368AN: 152190Hom.: 55 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00497 AC: 1247AN: 251092Hom.: 23 AF XY: 0.00385 AC XY: 523AN XY: 135730
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GnomAD4 exome AF: 0.00257 AC: 3754AN: 1461804Hom.: 61 Cov.: 32 AF XY: 0.00233 AC XY: 1698AN XY: 727208
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GnomAD4 genome ? AF: 0.0157 AC: 2395AN: 152308Hom.: 57 Cov.: 33 AF XY: 0.0149 AC XY: 1107AN XY: 74480
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ESP6500AA
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703
Asia WGS
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3478
ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 10, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Tyrosinase-positive oculocutaneous albinism Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MVP
MPC
0.11
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at