rs1800415
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_000275.3(OCA2):c.1887G>T(p.Val629=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,614,058 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.010 ( 28 hom., cov: 33)
Exomes 𝑓: 0.00097 ( 22 hom. )
Consequence
OCA2
NM_000275.3 synonymous
NM_000275.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.439
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 -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BP6
?
Variant 15-27951848-C-A is Benign according to our data. Variant chr15-27951848-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 255725.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.439 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0101 (1541/152300) while in subpopulation AFR AF= 0.0348 (1447/41560). AF 95% confidence interval is 0.0333. There are 28 homozygotes in gnomad4. There are 727 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 28 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OCA2 | NM_000275.3 | c.1887G>T | p.Val629= | synonymous_variant | 18/24 | ENST00000354638.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OCA2 | ENST00000354638.8 | c.1887G>T | p.Val629= | synonymous_variant | 18/24 | 1 | NM_000275.3 | P1 | |
OCA2 | ENST00000353809.9 | c.1815G>T | p.Val605= | synonymous_variant | 17/23 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0101 AC: 1538AN: 152182Hom.: 28 Cov.: 33
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GnomAD3 exomes AF: 0.00270 AC: 680AN: 251416Hom.: 12 AF XY: 0.00206 AC XY: 280AN XY: 135884
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GnomAD4 exome AF: 0.000966 AC: 1412AN: 1461758Hom.: 22 Cov.: 31 AF XY: 0.000799 AC XY: 581AN XY: 727190
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GnomAD4 genome ? AF: 0.0101 AC: 1541AN: 152300Hom.: 28 Cov.: 33 AF XY: 0.00976 AC XY: 727AN XY: 74470
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely 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 | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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