15-27989645-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The NM_000275.3(OCA2):c.1138G>A(p.Val380Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000161 in 1,614,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V380L) has been classified as Uncertain significance.
Frequency
Consequence
NM_000275.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OCA2 | NM_000275.3 | c.1138G>A | p.Val380Met | missense_variant | 11/24 | ENST00000354638.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OCA2 | ENST00000354638.8 | c.1138G>A | p.Val380Met | missense_variant | 11/24 | 1 | NM_000275.3 | P1 | |
OCA2 | ENST00000353809.9 | c.1066G>A | p.Val356Met | missense_variant | 10/23 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152186Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251406Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135886
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461846Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 727218
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74354
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 13, 2022 | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 380 of the OCA2 protein (p.Val380Met). This variant is present in population databases (rs41529845, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with OCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1013061). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at