Submissions for variant NM_000350.3(ABCA4):c.5196+1G>A

gnomAD frequency: 0.00001  dbSNP: rs61751377

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV000408528	SCV000281916	pathogenic	Severe early-childhood-onset retinal dystrophy	2016-01-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000085704	SCV000329048	pathogenic	not provided	2022-02-08	criteria provided, single submitter	clinical testing	Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 10958763, 9666097, 16103129, 9295268, 25097241, 9973280, 11379881, 11818392, 26103963, 26161775, 27739528, 28118664, 30204727, 29925512, 31589614, 32619608, 34426522, 32845068, 33090715, 33301772, 33261146, 25525159, 31736247)
Invitae	RCV000085704	SCV001229080	pathogenic	not provided	2024-01-29	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 36 of the ABCA4 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 ABCA4 are known to be pathogenic (PMID: 10958761, 24938718, 25312043, 26780318). 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 retinal disease (PMID: 16103129, 25097241, 27739528, 28118664). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as 36IVS+1G>A. ClinVar contains an entry for this variant (Variation ID: 99351). 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.
Blueprint Genetics	RCV001074902	SCV001240506	pathogenic	Retinal dystrophy	2019-08-16	criteria provided, single submitter	clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001197154	SCV001367790	pathogenic	Age related macular degeneration 2	2019-02-24	criteria provided, single submitter	clinical testing	This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2,PP3,PP5.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000085704	SCV001447242	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Ocular Genomics Institute, Massachusetts Eye and Ear	RCV000408528	SCV001573563	pathogenic	Severe early-childhood-onset retinal dystrophy	2021-04-08	criteria provided, single submitter	research	The ABCA4 c.5196+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: PM2, PVS1, PP3, PM3, PS3. Based on this evidence we have classified this variant as Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV000085704	SCV002496897	pathogenic	not provided	2024-01-01	criteria provided, single submitter	clinical testing	ABCA4: PM3:Very Strong, PVS1, PM2, PP4, PS3:Supporting
Retina International	RCV000085704	SCV000117844	not provided	not provided		no assertion provided	not provided
Sharon lab, Hadassah-Hebrew University Medical Center	RCV001002818	SCV001160833	pathogenic	maculopathy	2019-06-23	no assertion criteria provided	research