ClinVar Miner

Submissions for variant NM_147127.5(EVC2):c.3659+2T>C (rs200300612)

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
Illumina Clinical Services Laboratory,Illumina RCV000665483 SCV000449971 likely pathogenic Ellis-van Creveld syndrome 2016-09-18 criteria provided, single submitter clinical testing The EVC2 c.3659+2T>C variant, also known as IVS21+2T>C, occurs in a canonical splice donor site and is therefore predicted to disrupt or distort the normal gene product. The variant has been reported in three studies in which it is found in a total of three individuals with Ellis-van Creveld syndrome, all in a compound heterozygous state with truncating variants on the second allele (Tompson et al. 2007; Sund et al. 2009; D'Asdia et al. 2013). The c.3659+2T>C variant was absent from 400 control chromosomes and is reported at a frequency of 0.00006 in the European (non-Finnish) population of the Exome Aggregation Consortium. Based on the evidence and the potential impact of splice donor variants, the c.3659+2T>C variant is classified as likely pathogenic for Ellis-van Creveld syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
GeneDx RCV000521259 SCV000617820 pathogenic not provided 2021-05-25 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in an in-frame deletion/insertion of a critical region; This variant is associated with the following publications: (PMID: 25525159, 19876929, 23220543, 19251731, 17024374, 31589614)
Invitae RCV000695869 SCV000824393 likely pathogenic Ellis-van Creveld syndrome; Curry-Hall syndrome 2020-08-03 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in the last intron (intron 21) of the EVC2 gene. While this 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 (rs200300612, ExAC 0.006%). This variant has been observed in individuals affected with Ellis-van Creveld syndrome (PMID: 17024374, 23220543, Invitae). ClinVar contains an entry for this variant (Variation ID: 348980). Nucleotide substitutions within 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, 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.
Counsyl RCV000665483 SCV000789613 pathogenic Ellis-van Creveld syndrome 2017-02-13 no assertion criteria provided clinical testing

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.