Submissions for variant NM_153717.3(EVC):c.1777-2A>G

gnomAD frequency: 0.00001  dbSNP: rs909612975

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000666935	SCV000791310	likely pathogenic	Ellis-van Creveld syndrome	2017-05-15	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001229451	SCV001401896	pathogenic	Ellis-van Creveld syndrome; Curry-Hall syndrome	2023-12-03	criteria provided, single submitter	clinical testing	This sequence change affects an acceptor splice site in intron 12 of the EVC 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 EVC are known to be pathogenic (PMID: 23220543). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. Disruption of this splice site has been observed in individuals with Ellis-van Creveld syndrome (PMID: 17024374, 23220543). This variant is also known as IVS12-2A > G. ClinVar contains an entry for this variant (Variation ID: 551792). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV003432723	SCV004147615	pathogenic	not provided	2022-10-01	criteria provided, single submitter	clinical testing	EVC: PVS1, PM2
Natera, Inc.	RCV000666935	SCV002083041	pathogenic	Ellis-van Creveld syndrome	2020-04-27	no assertion criteria provided	clinical testing