@conference{
author = "Mijović, Marija and Cuturilo, Goran and Ruml Stojanović, Jelena and Miletić, Aleksandra and Bosankić, Brankica and Petrović, Hristina and Vasić, Bojana and Vukasinović, Nađa",
year = "2023",
abstract = "ACMG recognizes five different categories of sequence variants identified by next
generation sequencing (pathogenic, likely pathogenic, variants of unknown significance,
likely benign and benign). Sometimes, potentially relevant gene variants could be
categorized as variants of unknown significance according to the level of available
evidences. Because of that, detailed assessment of the phenotype-genotype correlation
by the clinical geneticist in each individual case is crucially important. The interpretation
and classification of a variant may change over time. Variant reinterpretation is defined as
the practice of reevaluating all the evidence available about the pathogenicity of a genetic
variant and taking into account any new evidence that is made available since the previous
interpretation.
For the last seven years, we had 168 patients with clinically suspected locus heterogeneous
skeletal dysplasia. Next generation sequencing (NGS) using clinical exome sequencing
or whole exome sequencing was performed for all. All patients underwent detailed
phenotype-genotype correlation investigation.
Molecular diagnosis by determining the pathogenic or likely pathogenic causative gene
variant(s) was established for 102 out of 168 patients (60.71%). Additionally, in 10 patients
(5.95%) variant of unknown significance (VUS) with good phenotype-genotype correlation
was identified. These VUS variants could be potentially, and possibly are, causal, although
there are no reliable evidences of their pathogenicity at the moment. In one of the positive
patients in our study, the variant was initially classified as VUS, but with new evidence it
was reclassified as likely pathogenic.
In the present study, a potentially relevant variant of unknown significance was detected
in 5.95% of patients, which is a non-negligible proportion. For all these patients, we have
organized clinical follow-up with periodic reinterpretation and reclassification of the
detected variants.",
publisher = "Belgrade : Institute of molecular genetics and genetic engineering",
journal = "4th Belgrade Bioinformatics Conference",
title = "Potentially relevant variants of unknown significance in NGS-tested patients with suspected skeletal dysplasia",
pages = "110-110",
volume = "4",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2055"
}
