rs373775562
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP7
The NM_000275.3(OCA2):c.1080C>T(p.Ser360=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,613,932 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
OCA2
NM_000275.3 synonymous
NM_000275.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.329
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 Likely_benign. Variant got -5 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP7
Synonymous conserved (PhyloP=0.329 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OCA2 | NM_000275.3 | c.1080C>T | p.Ser360= | synonymous_variant | 10/24 | ENST00000354638.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OCA2 | ENST00000354638.8 | c.1080C>T | p.Ser360= | synonymous_variant | 10/24 | 1 | NM_000275.3 | P1 | |
OCA2 | ENST00000353809.9 | c.1045-946C>T | intron_variant | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152164Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251144Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135748
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GnomAD4 exome AF: 0.0000178 AC: 26AN: 1461768Hom.: 0 Cov.: 30 AF XY: 0.0000193 AC XY: 14AN XY: 727182
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152164Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74342
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Tyrosinase-positive oculocutaneous albinism Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Laboratoire de Génétique Moléculaire, CHU Bordeaux | - | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 09, 2024 | This sequence change affects codon 360 of the OCA2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the OCA2 protein. This variant is present in population databases (rs373775562, gnomAD 0.004%). This variant has been observed in individual(s) with clinical features of oculocutaneous albinism (PMID: 37650133; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 255717). Studies have shown that this variant is associated with inconclusive levels of altered splicing (PMID: 37650133). For these reasons, this variant has been classified as Pathogenic. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at