Submissions for variant NM_015662.3(IFT172):c.184-2A>C

dbSNP: rs2148559396

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002035036	SCV002113479	likely pathogenic	Short-rib thoracic dysplasia 10 with or without polydactyly; Retinitis pigmentosa 71	2020-11-12	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals with IFT172-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 2 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). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
PreventionGenetics, part of Exact Sciences	RCV004552055	SCV004121042	likely pathogenic	IFT172-related disorder	2023-09-01	criteria provided, single submitter	clinical testing	The IFT172 c.184-2A>C variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Variants that disrupt the consensus splice acceptor site in IFT172 are expected to be pathogenic. This variant is interpreted as likely pathogenic.