Submissions for variant NM_000330.4(RS1):c.52+3A>G

dbSNP: rs2147209764

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Molecular Genetics, Royal Melbourne Hospital	RCV001733782	SCV002503696	likely pathogenic	Juvenile retinoschisis	2023-03-30	criteria provided, single submitter	clinical testing	This sequence change falls in the splice region of the donor site of intron 1 of RS1. The variant is absent in a large population cohort (gnomAD v2.1), and has been identified in at least four male cases with a clinical diagnosis of retinoschisis (Royal Melbourne Hospital;PMID: 31725702). The nucleotide is conserved to mammals (100 vertebrates, UCSC), and multiple lines of computational evidence predict a impact on splicing (HSF, MaxEntScan, NNSplice). The predicted splicing aberration is expected to lead to loss or truncation of the protein, but has not been confirmed with patient RNA studies. Based on the classification scheme RMH ACMG Guidelines v1.2.1, this variant is classified as LIKELY PATHOGENIC. Following criteria are met: PS4, PM2, PP3.
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	RCV004798926	SCV002818197	likely pathogenic	Retinoschisis	2024-10-04	criteria provided, single submitter	research	PM3, PM2, PP3, PP4
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	RCV001733782	SCV001984700	uncertain significance	Juvenile retinoschisis	2020-09-13	flagged submission	clinical testing