Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory of Medical Genetics |
RCV000757977 | SCV000839872 | pathogenic | Bardet-Biedl syndrome | 2018-09-15 | criteria provided, single submitter | clinical testing | Mutation affecting splicing (functional study in submitter's publication) |
Invitae | RCV001035042 | SCV001198350 | pathogenic | not provided | 2024-01-06 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 5 of the IFT27 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs780659194, gnomAD 0.02%). Disruption of this splice site has been observed in individual(s) with clinical features of IFT27-related conditions (PMID: 29704304, 30761183). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as c.352+1G>T. ClinVar contains an entry for this variant (Variation ID: 585274). Studies have shown that disruption of this splice site results in skipping of exons 4-5 and 4-6, but is expected to preserve the integrity of the reading-frame (PMID: 30761183). For these reasons, this variant has been classified as Pathogenic. |
Prevention |
RCV003392548 | SCV004120120 | likely pathogenic | IFT27-related disorder | 2022-10-20 | criteria provided, single submitter | clinical testing | The IFT27 c.349+1G>T variant is predicted to disrupt the GT donor site and interfere with normal splicing. On an alternate transcript (NM_001177701.2), this variant is referred to as c.352+1G>T. This variant was reported in the compound heterozygous state in two individuals with features consistent with Bardet-Biedl syndrome (Schaefer et al. 2019. PubMed ID: 30761183; Quélin et al. 2018. PubMed ID: 29704304). This variant is reported in 0.019% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/22-37159962-C-A). Variants that disrupt the consensus splice donor site in IFT27 are expected to be pathogenic. This variant is interpreted as likely pathogenic. |
OMIM | RCV001537637 | SCV001754537 | pathogenic | Bardet-Biedl syndrome 19 | 2021-07-16 | no assertion criteria provided | literature only |