Submissions for variant NM_000350.3(ABCA4):c.5044_5058del (p.Val1682_Val1686del)

dbSNP: rs62646872

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Mendelics	RCV000986352	SCV001135335	pathogenic	Severe early-childhood-onset retinal dystrophy	2019-05-28	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV001073680	SCV001239233	pathogenic	Retinal dystrophy	2019-08-15	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000085693	SCV001374725	pathogenic	not provided	2025-01-13	criteria provided, single submitter	clinical testing	This variant, c.5044_5058del, results in the deletion of 5 amino acid(s) of the ABCA4 protein (p.Val1682_Val1686del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs767421372, gnomAD 0.02%). This variant has been observed in individual(s) with autosomal recessive retinal disease, commonly in cis with the pathogenic variant c.4926C>G (p.Ser1642Arg). This variant has also been observed without p.Ser1642Arg in individuals with autosomal recessive Stargardt disease or cone-rod dystrophy, and the evidence is sufficient to classify p.Val1682_Val1686del as Pathogenic in isolation, whether or not p.Ser1642Arg is present (PMID: 9054934, 23419329, 23755871, 29114839, 29186038, 30060493, 30093795). 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 4927del15 (delVVAIC1643). ClinVar contains an entry for this variant (Variation ID: 99340). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000085693	SCV001447934	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
3billion, Medical Genetics	RCV000986352	SCV002520979	pathogenic	Severe early-childhood-onset retinal dystrophy	2022-05-22	criteria provided, single submitter	clinical testing	The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.003%). Inframe deletion located in a nonrepeat region: predicted to change the length of the protein and disrupt normal protein function. The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 29186038, 30093795). The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000099340 / PMID: 9054934 / 3billion dataset). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Fulgent Genetics, Fulgent Genetics	RCV002498457	SCV002813974	pathogenic	Cone-rod dystrophy 3; Age related macular degeneration 2; Severe early-childhood-onset retinal dystrophy; Retinitis pigmentosa 19	2021-12-23	criteria provided, single submitter	clinical testing
Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel	RCV003324513	SCV004030327	pathogenic	Stargardt disease	2023-07-24	criteria provided, single submitter	research	Clinical significance based on ACMG v2.0
Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel	RCV003324512	SCV004030338	pathogenic	Cone-rod dystrophy	2023-07-24	criteria provided, single submitter	research	Clinical significance based on ACMG v2.0
Retina International	RCV000085693	SCV000117833	not provided	not provided		no assertion provided	not provided
Ophthalmo-Genetics Lab, Instituto de Oftalmologia Conde de Valenciana	RCV000986352	SCV005047043	pathogenic	Severe early-childhood-onset retinal dystrophy		no assertion criteria provided	research