Submissions for variant NM_033100.4(CDHR1):c.863-1G>A

dbSNP: rs886041900

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000376892	SCV000330696	pathogenic	not provided	2017-01-31	criteria provided, single submitter	clinical testing	The c.863-1G>A pathogenic variant in the CDHR1 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 acceptor site in intron 9. 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.863-1G>A variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.863-1G>A as a pathogenic variant.
Ocular Genomics Institute, Massachusetts Eye and Ear	RCV001376330	SCV001573438	likely pathogenic	Cone-rod dystrophy 15	2021-04-08	criteria provided, single submitter	research	The CDHR1 c.863-1G>A variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PVS1, PM2. Based on this evidence we have classified this variant as Likely Pathogenic.
Invitae	RCV000376892	SCV004385990	likely pathogenic	not provided	2023-07-03	criteria provided, single submitter	clinical testing	This sequence change affects an acceptor splice site in intron 9 of the CDHR1 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 CDHR1 are known to be pathogenic (PMID: 23044944, 23591405, 26103963, 26261414). This variant is present in population databases (no rsID available, gnomAD 0.003%). Disruption of this splice site has been observed in individual(s) with clinical features of retinitis pigmentosa (Invitae). ClinVar contains an entry for this variant (Variation ID: 280752). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.