Submissions for variant NM_201548.5(CERKL):c.481+2T>G

gnomAD frequency: 0.00002  dbSNP: rs753994107

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000626729	SCV000747432	pathogenic	Cone dystrophy; Retinal pigment epithelial atrophy	2017-01-01	criteria provided, single submitter	clinical testing
Mendelics	RCV000986950	SCV001136110	likely pathogenic	Retinitis pigmentosa 26	2022-10-21	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001093154	SCV001250002	pathogenic	not provided	2024-03-01	criteria provided, single submitter	clinical testing	CERKL: PM3:Strong, PVS1:Strong, PM2
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000986950	SCV001366524	pathogenic	Retinitis pigmentosa 26	2016-01-01	criteria provided, single submitter	clinical testing	This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PS1,PP3.
Invitae	RCV001093154	SCV002272829	pathogenic	not provided	2024-01-29	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 2 of the CERKL 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 CERKL are known to be pathogenic (PMID: 14681825, 23591405, 24043777). 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 individual(s) with clinical features of CERKL-related conditions (PMID: 23591405, 28838317, 30718709, 32531858, 33921607). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 523393). 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.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000787562	SCV004023414	likely pathogenic	Retinitis pigmentosa	2023-08-09	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000986950	SCV004211603	likely pathogenic	Retinitis pigmentosa 26	2023-03-02	criteria provided, single submitter	clinical testing
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	RCV000787562	SCV000926538	likely pathogenic	Retinitis pigmentosa	2018-04-01	no assertion criteria provided	research