ClinVar Miner

Submissions for variant NM_025103.4(IFT74):c.1685-1G>T

gnomAD frequency: 0.00005  dbSNP: rs200699377
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Medicine Lab, University of California San Francisco RCV000240867 SCV001547493 likely pathogenic Bardet-Biedl syndrome 22 2020-05-14 criteria provided, single submitter clinical testing The IFT74 gene encodes an intraflagellar transport protein that is involved in transport of ciliary proteins along the axonemal microtubules. Variants in this gene are associated with Bardet-Biedl syndrome 20 (MIM#617119), an autosomal recessive disorder characterized by retinitis pigmentosa, obesity, polydactyly, hypogonadism, and intellectual disability. This specific splice site variant has been described once before (PMID: 27486776). There is a Clinvar entry for this variant (Variant ID: 254276). This variant is present in population databases, with an allele frequency of 0.0021% in gnomAD (5 heterozygotes).
Invitae RCV002518558 SCV003294354 uncertain significance not provided 2022-07-13 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 19 of the IFT74 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is present in population databases (rs200699377, gnomAD 0.005%). Disruption of this splice site has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 27486776, 32144365, 33748949). This variant is also known as c.16850–1G>T. ClinVar contains an entry for this variant (Variation ID: 254276). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
PreventionGenetics, part of Exact Sciences RCV003409371 SCV004113348 likely pathogenic IFT74-related disorder 2022-11-23 criteria provided, single submitter clinical testing The IFT74 c.1685-1G>T variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. This variant has been previously reported in the homozygous or compound heterozygous state in individuals with Bardet-Biedl syndrome (Lindstrand et al. 2016. PubMed ID: 27486776; Kleinendorst et al. 2020. PubMed ID: 32144365; Mardy et al. 2021. PubMed ID: 33748949). This variant is reported in 0.0048% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-27062615-G-T). Variants that disrupt the consensus splice acceptor site in IFT74 are expected to be pathogenic. This variant is interpreted as likely pathogenic.
OMIM RCV000240867 SCV000299366 pathogenic Bardet-Biedl syndrome 22 2021-10-21 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.