ClinVar Miner

Submissions for variant NM_000275.3(OCA2):c.1109T>C (p.Ile370Thr)

gnomAD frequency: 0.00369  dbSNP: rs34731820
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766740 SCV000568222 uncertain significance not provided 2017-01-26 criteria provided, single submitter clinical testing The I370T variant in the OCA2 gene has been reported previously in two unrelated individuals of African descent with an unusual hypopigmentation phenotype suggestive of oculocutaneous albinism (OCA). The I370T variant was reported along with a second variant in an individual with light brown eyes and yellow-ish white colored hair. The second individual was heterozygous for the I370T variant, with no second variant identified, and had reddish-brown colored skin (Kerr et al., 2000). The I370T variant is observed in 114/10360 (1.1%) alleles from individuals of African background in the ExAC dataset, and no individuals were reported to be homozygous (Lek et al., 2016). The I370T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where amino acids with similar properties to Isoleucine are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret I370T as a variant of uncertain significance.
Genetic Services Laboratory, University of Chicago RCV000483390 SCV000596147 likely benign not specified 2015-10-20 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000778423 SCV000914662 uncertain significance Tyrosinase-positive oculocutaneous albinism 2017-12-12 criteria provided, single submitter clinical testing The OCA2 c.1109T>C (p.Ile370Thr) missense variant has been reported in one study in which it was found in a compound heterozygous state with a second missense variant in one individual with an unusual hypopigmentation type, and in a heterozygous state in another individual with a skin color resembling that of rufus oculocutaneous albinism, in whom a second variant was not detected (Kerr et al. 2000). The Ile370 residue is conserved. Control data are unavailable for this variant, which is reported at a frequency of 0.025253 in the Esan in Nigeria population of the 1000 Genomes Project. Based on the evidence, the p.Ile370Thr variant is classified as a variant of uncertain significance but suspicious for pathogenicity for oculocutaneous albinism. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000766740 SCV001724505 benign not provided 2024-01-29 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000778423 SCV002040048 uncertain significance Tyrosinase-positive oculocutaneous albinism 2021-11-07 criteria provided, single submitter clinical testing

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