Submissions for variant NM_006915.3(RP2):c.969+2T>C

dbSNP: rs1925392056

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001347060	SCV001541301	pathogenic	not provided	2023-07-14	criteria provided, single submitter	clinical testing	Variants that disrupt 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. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the RP2 protein in which other variant(s) (Deletion (Exon 5)) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 1043015). Disruption of this splice site has been observed in individuals with retinitis pigmentosa (PMID: 31736247; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 4 of the RP2 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product.
Ocular Genomics Institute, Massachusetts Eye and Ear	RCV001376363	SCV001573480	likely pathogenic	Retinitis pigmentosa 2	2021-04-08	criteria provided, single submitter	research	The RP2 c.969+2T>C variant was identified in an individual with retinitis pigmentosa with a presumed X-linked 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.