rs137956605
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_000275.3(OCA2):c.1153T>A(p.Phe385Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000325 in 1,614,178 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000275.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OCA2 | ENST00000354638.8 | c.1153T>A | p.Phe385Ile | missense_variant | Exon 11 of 24 | 1 | NM_000275.3 | ENSP00000346659.3 | ||
OCA2 | ENST00000353809.9 | c.1081T>A | p.Phe361Ile | missense_variant | Exon 10 of 23 | 1 | ENSP00000261276.8 |
Frequencies
GnomAD3 genomes AF: 0.00198 AC: 301AN: 152186Hom.: 4 Cov.: 32
GnomAD3 exomes AF: 0.000485 AC: 122AN: 251398Hom.: 2 AF XY: 0.000397 AC XY: 54AN XY: 135878
GnomAD4 exome AF: 0.000153 AC: 223AN: 1461874Hom.: 0 Cov.: 32 AF XY: 0.000131 AC XY: 95AN XY: 727236
GnomAD4 genome AF: 0.00198 AC: 301AN: 152304Hom.: 4 Cov.: 32 AF XY: 0.00171 AC XY: 127AN XY: 74476
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
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Previously reported in the published literature in a patient with OCA type 2 who also harbored a second OCA2 variant, however parental studies were not performed to determine the phase of these two variants, and functional studies were not performed (Lee et al., 1994); Observed in 184/282774 (0.065%) alleles in large population cohorts, and multiple individuals were reported to be homozygous (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25525159, 7874125) -
not specified Uncertain:1
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Tyrosinase-positive oculocutaneous albinism Uncertain:1
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OCA2-related disorder Uncertain:1
The OCA2 c.1153T>A variant is predicted to result in the amino acid substitution p.Phe385Ile. This variant has been reported along with a 2nd OCA2 variant an individual with oculocutaneous albinism (Lee et al 1994. PubMed ID: 7874125). This variant is reported in 0.70% of alleles in individuals of African descent in gnomAD, including three homozygotes (http://gnomad.broadinstitute.org/variant/15-28234776-A-T), indicating it is fairly common in this population. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at