ClinVar Miner

Submissions for variant NM_021728.4(OTX2):c.425C>G (p.Pro142Arg)

gnomAD frequency: 0.00016  dbSNP: rs199761861
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000989232 SCV001139467 uncertain significance Syndromic microphthalmia type 5 2019-05-28 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001113289 SCV001271051 uncertain significance Pituitary hormone deficiency, combined, 6 2017-04-27 criteria provided, single submitter clinical testing 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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001215155 SCV001386884 uncertain significance Anophthalmia-microphthalmia syndrome 2023-12-11 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 134 of the OTX2 protein (p.Pro134Arg). This variant is present in population databases (rs199761861, gnomAD 0.05%), including at least one homozygous and/or hemizygous individual. This missense change has been observed in individual(s) with combined pituitary hormone deficiency and left optic nerve hypoplasia (PMID: 22715480). ClinVar contains an entry for this variant (Variation ID: 803030). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Experimental studies have shown that this missense change affects OTX2 function (PMID: 22715480). 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.
GeneDx RCV001840779 SCV002099569 likely pathogenic not provided 2023-03-22 criteria provided, single submitter clinical testing Published functional studies demonstrate decreased transactivation activity (Gorbenko Del Blanco et al., 2012); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22715480, 23990694, 34426522, 33296094)
Laan Lab, Human Genetics Research Group, University of Tartu RCV002254530 SCV002525860 likely pathogenic 46,XY partial gonadal dysgenesis 2020-08-01 criteria provided, single submitter research
Institute of Human Genetics, University of Leipzig Medical Center RCV000989232 SCV004027779 uncertain significance Syndromic microphthalmia type 5 2023-06-29 criteria provided, single submitter clinical testing Criteria applied: PS4_MOD,PS3_SUP,PM5_SUP,PP3
Laan Lab, Human Genetics Research Group, University of Tartu RCV003991583 SCV004239168 likely pathogenic Male infertility with azoospermia or oligozoospermia due to single gene mutation 2023-09-01 criteria provided, single submitter research

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