Submissions for variant NM_000350.3(ABCA4):c.4539+2064C>T

dbSNP: rs1553189179

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000994041	SCV000721498	likely pathogenic	not provided	2022-01-04	criteria provided, single submitter	clinical testing	Published functional studies suggest this variant results in impairment of gene splicing, however the significance is unclear relative to the normal splicing product (Bauwens et al., 2019); In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; No data available from control populations to assess the frequency of this variant; This variant is associated with the following publications: (PMID: 25082829, 28005958, 31212395, 32278709, 33546218, 31614660, 32619608, 30670881)
CeGaT Center for Human Genetics Tuebingen	RCV000994041	SCV001147333	pathogenic	not provided	2023-01-01	criteria provided, single submitter	clinical testing	ABCA4: PM3:Very Strong, PM2, PP4, PS3:Supporting
Institute of Medical Molecular Genetics, University of Zurich	RCV001352957	SCV001548028	likely pathogenic	Severe early-childhood-onset retinal dystrophy	2021-01-30	criteria provided, single submitter	clinical testing
Invitae	RCV000994041	SCV001579214	pathogenic	not provided	2023-11-27	criteria provided, single submitter	clinical testing	This sequence change falls in intron 30 of the ABCA4 gene. It does not directly change the encoded amino acid sequence of the ABCA4 protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with Stargardt disease (PMID: 31614660). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 511074). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic.
Clinical Genetics, Academic Medical Center	RCV000994041	SCV001920846	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000994041	SCV001955301	likely pathogenic	not provided		no assertion criteria provided	clinical testing