Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Fulgent Genetics, |
RCV002492710 | SCV002797971 | likely pathogenic | Short-rib thoracic dysplasia 10 with or without polydactyly; Retinitis pigmentosa 71; Bardet-Biedl syndrome 20 | 2022-05-05 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002515241 | SCV003283954 | pathogenic | Short-rib thoracic dysplasia 10 with or without polydactyly; Retinitis pigmentosa 71 | 2024-11-05 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 15 of the IFT172 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in IFT172 are known to be pathogenic (PMID: 24140113). This variant is present in population databases (rs370540673, gnomAD 0.002%). Disruption of this splice site has been observed in individual(s) with IFT172-related conditions (PMID: 25168386). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 191367). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV004562395 | SCV000223725 | pathogenic | Bardet-Biedl syndrome 20 | 2015-01-01 | no assertion criteria provided | literature only | |
Prevention |
RCV004737264 | SCV005347348 | pathogenic | IFT172-related disorder | 2024-06-28 | no assertion criteria provided | clinical testing | The IFT172 c.1525-1G>A variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. This variant has been reported in the compound heterozygous state in two siblings with retinitis pigmentosa (Family 1, Bujakowska et al. 2015. PubMed ID: 25168386). This variant is reported in 0.0018% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Variants that disrupt the consensus splice acceptor site in IFT172 are expected to be pathogenic. This variant is interpreted as pathogenic. |