Submissions for variant NM_000350.3(ABCA4):c.4849-1G>A

gnomAD frequency: 0.00001  dbSNP: rs61750156

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Blueprint Genetics	RCV001074206	SCV001239778	pathogenic	Retinal dystrophy	2019-03-15	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001235111	SCV001407781	pathogenic	not provided	2024-12-23	criteria provided, single submitter	clinical testing	This sequence change affects an acceptor splice site in intron 34 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). This variant is present in population databases (rs61750156, gnomAD 0.006%). Disruption of this splice site has been observed in individuals with ABCA4-related conditions (internal data). ClinVar contains an entry for this variant (Variation ID: 866320). 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.
GeneDx	RCV001235111	SCV001823164	pathogenic	not provided	2019-05-07	criteria provided, single submitter	clinical testing	Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics	RCV005029679	SCV005658831	likely pathogenic	Cone-rod dystrophy 3; Age related macular degeneration 2; Severe early-childhood-onset retinal dystrophy; Retinitis pigmentosa 19	2024-04-02	criteria provided, single submitter	clinical testing
Ophthalmo-Genetics Lab, Instituto de Oftalmologia Conde de Valenciana	RCV004564575	SCV005047035	pathogenic	Severe early-childhood-onset retinal dystrophy		no assertion criteria provided	research
PreventionGenetics, part of Exact Sciences	RCV004733150	SCV005361506	likely pathogenic	ABCA4-related disorder	2024-04-12	no assertion criteria provided	clinical testing	The ABCA4 c.4849-1G>A variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. This variant has not been reported in literature. This variant is reported in 0.0058% of alleles in individuals of Latino descent in gnomAD. Variants that disrupt the consensus splice acceptor site in ABCA4 are expected to be pathogenic. This variant is interpreted as likely pathogenic.