Submissions for variant NM_000096.4(CP):c.607+1del

dbSNP: rs753254095

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000489374	SCV000577358	likely pathogenic	not provided	2017-04-03	criteria provided, single submitter	clinical testing	The c.607+1delG variant in the CP gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This splice site variant destroys the canonical splice donor site in intron 3. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.607+1delG variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.607+1delG as a likely pathogenic variant.
Invitae	RCV001856906	SCV002237179	pathogenic	Deficiency of ferroxidase	2021-06-01	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. 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. This variant has not been reported in the literature in individuals with CP-related conditions. This variant is also known as c.607+1del. ClinVar contains an entry for this variant (Variation ID: 426814). This variant is present in population databases (rs753254095, ExAC 0.03%). This sequence change creates a premature translational stop signal (p.Asp203Ilefs*3) in the CP gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CP are known to be pathogenic (PMID: 16629161).