Potentially relevant variants of unknown significance in NGS-tested patients with suspected skeletal dysplasia
Autori
Mijović, MarijaCuturilo, Goran
Ruml Stojanović, Jelena
Miletić, Aleksandra
Bosankić, Brankica
Petrović, Hristina
Vasić, Bojana
Vukasinović, Nađa
Ostala autorstva
Morić, IvanaĐorđević, Valentina
Konferencijski prilog (Objavljena verzija)
,
© 2023 Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
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.
Ključne reči:
next generation sequencing / variant(s) of unknown significance / classification / reinterpretation / reclassification / skeletal dysplasiaIzvor:
4th Belgrade Bioinformatics Conference, 2023, 4, 110-110Izdavač:
- Belgrade : Institute of molecular genetics and genetic engineering
Napomena:
- Book of abstract: 4th Belgrade Bioinformatics Conference, June 19-23, 2023
Kolekcije
Institucija/grupa
Institut za molekularnu genetiku i genetičko inženjerstvoTY - CONF AU - Mijović, Marija AU - Cuturilo, Goran AU - Ruml Stojanović, Jelena AU - Miletić, Aleksandra AU - Bosankić, Brankica AU - Petrović, Hristina AU - Vasić, Bojana AU - Vukasinović, Nađa PY - 2023 UR - https://belbi.bg.ac.rs/ UR - https://imagine.imgge.bg.ac.rs/handle/123456789/2055 AB - 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. PB - Belgrade : Institute of molecular genetics and genetic engineering C3 - 4th Belgrade Bioinformatics Conference T1 - Potentially relevant variants of unknown significance in NGS-tested patients with suspected skeletal dysplasia EP - 110 SP - 110 VL - 4 UR - https://hdl.handle.net/21.15107/rcub_imagine_2055 ER -
@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" }
Mijović, M., Cuturilo, G., Ruml Stojanović, J., Miletić, A., Bosankić, B., Petrović, H., Vasić, B.,& Vukasinović, N.. (2023). Potentially relevant variants of unknown significance in NGS-tested patients with suspected skeletal dysplasia. in 4th Belgrade Bioinformatics Conference Belgrade : Institute of molecular genetics and genetic engineering., 4, 110-110. https://hdl.handle.net/21.15107/rcub_imagine_2055
Mijović M, Cuturilo G, Ruml Stojanović J, Miletić A, Bosankić B, Petrović H, Vasić B, Vukasinović N. Potentially relevant variants of unknown significance in NGS-tested patients with suspected skeletal dysplasia. in 4th Belgrade Bioinformatics Conference. 2023;4:110-110. https://hdl.handle.net/21.15107/rcub_imagine_2055 .
Mijović, Marija, Cuturilo, Goran, Ruml Stojanović, Jelena, Miletić, Aleksandra, Bosankić, Brankica, Petrović, Hristina, Vasić, Bojana, Vukasinović, Nađa, "Potentially relevant variants of unknown significance in NGS-tested patients with suspected skeletal dysplasia" in 4th Belgrade Bioinformatics Conference, 4 (2023):110-110, https://hdl.handle.net/21.15107/rcub_imagine_2055 .