ClinVar Miner

Submissions for variant NM_016111.4(TELO2):c.2296G>A (p.Val766Met)

gnomAD frequency: 0.00010  dbSNP: rs371675497
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor-Hopkins Center for Mendelian Genomics, Johns Hopkins University School of Medicine RCV000225221 SCV000298026 pathogenic TELO2-related intellectual disability-neurodevelopmental disorder criteria provided, single submitter research
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000225221 SCV000930175 uncertain significance TELO2-related intellectual disability-neurodevelopmental disorder 2019-04-27 criteria provided, single submitter clinical testing
GeneDx RCV001589164 SCV001827142 uncertain significance not provided 2021-05-20 criteria provided, single submitter clinical testing Reported previously in an individual with intellectual disability, developmental delay, seizures, and microcephaly who was compound heterozygous for another missense variant; in vitro studies of cells derived from this patient demonstrated a decreased amount of TELO2 protein (You et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 31290144, 27132593, 32940098)
Genetic Services Laboratory, University of Chicago RCV001814974 SCV002062021 uncertain significance not specified 2018-07-24 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001589164 SCV002286471 likely pathogenic not provided 2022-08-23 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TELO2 protein function. ClinVar contains an entry for this variant (Variation ID: 236227). This missense change has been observed in individual(s) with You-Hoover-Fong syndrome (PMID: 27132593). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs371675497, gnomAD 0.02%). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 766 of the TELO2 protein (p.Val766Met).
Mendelics RCV000225221 SCV002519859 pathogenic TELO2-related intellectual disability-neurodevelopmental disorder 2022-05-04 criteria provided, single submitter clinical testing
OMIM RCV000225221 SCV000282068 pathogenic TELO2-related intellectual disability-neurodevelopmental disorder 2019-09-10 no assertion criteria provided literature only

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