ClinVar Miner

Submissions for variant NM_052989.3(IFT122):c.3031G>C (p.Ala1011Pro)

gnomAD frequency: 0.00004  dbSNP: rs199622112
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
Invitae RCV001219619 SCV001391567 likely pathogenic Cranioectodermal dysplasia 1 2022-11-01 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt IFT122 protein function. ClinVar contains an entry for this variant (Variation ID: 948374). This missense change has been observed in individual(s) with clinical features of short-rib thoracic dysplasia (PMID: 28370949; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs199622112, gnomAD 0.01%). This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1062 of the IFT122 protein (p.Ala1062Pro).
Fulgent Genetics, Fulgent Genetics RCV001219619 SCV002782327 uncertain significance Cranioectodermal dysplasia 1 2021-09-07 criteria provided, single submitter clinical testing
GeneDx RCV003233996 SCV003931112 uncertain significance not provided 2022-12-09 criteria provided, single submitter clinical testing Observed with a second IFT122 variant, phase unknown, in a proband with craniosynostosis, micromelia, postaxial polydactyly of the hands, hydrops, and skeletal findings suggestive of short-rib polydactyly type IV (Silveira et al., 2017); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 19648123, 34529350, 28370949)
OMIM RCV001219619 SCV001441270 pathogenic Cranioectodermal dysplasia 1 2011-02-01 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.