Submissions for variant NM_000350.3(ABCA4):c.3602T>G (p.Leu1201Arg)

gnomAD frequency: 0.02895  dbSNP: rs61750126

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000176456	SCV000228115	benign	not specified	2015-03-05	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000343774	SCV000359391	likely benign	Cone-Rod Dystrophy, Recessive	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000401597	SCV000359392	likely benign	Macular degeneration	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000308786	SCV000359393	likely benign	Stargardt Disease, Recessive	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000340328	SCV000359394	likely benign	Retinitis Pigmentosa, Recessive	2016-06-14	criteria provided, single submitter	clinical testing
Mendelics	RCV000408567	SCV001135348	likely benign	Severe early-childhood-onset retinal dystrophy	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001096421	SCV001252629	likely benign	ABCA4-Related Disorders	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Invitae	RCV000085583	SCV001729889	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000085583	SCV001880968	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 28559085, 20647261, 29925512, 25066811, 24011517, 23982839, 27884173, 9973280, 25097241, 16123440, 19074458, 20981092)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000085583	SCV002047732	benign	not provided	2023-09-21	criteria provided, single submitter	clinical testing
OMIM	RCV000008361	SCV000028569	pathogenic	Cone-rod dystrophy 3	2003-06-01	flagged submission	literature only
Retina International	RCV000085583	SCV000117721	not provided	not provided		no assertion provided	not provided
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV000408567	SCV000281871	likely pathogenic	Severe early-childhood-onset retinal dystrophy	2016-01-01	flagged submission	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000176456	SCV001553447	benign	not specified		no assertion criteria provided	clinical testing	The ABCA4 p.Leu1201Arg variant was identified in 19 of 988 proband chromosomes (frequency: 0.019) from individuals or families with Stargardt disease and cone-rod dystrophy (Schulz_2017_PMID:28118664; Utz_2013_PMID:24011517; Zernant_2014_PMID:25066811; Fishman_2003_PMID:12796258). The variant was identified in dbSNP (ID: rs61750126), ClinVar (classified as benign by EGL Genetics, likely benign by Illumina and likely pathogenic by Institute of Human Genetics, Univ. Regensburg) and LOVD 3.0 (classified as a VUS and likely benign). The variant was also identified in control databases in 2402 of 266312 chromosomes (114 homozygous) at a frequency of 0.009019 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 2219 of 23326 chromosomes (freq: 0.09513), Other in 32 of 6916 chromosomes (freq: 0.004627), Latino in 133 of 34270 chromosomes (freq: 0.003881), European (non-Finnish) in 16 of 120738 chromosomes (freq: 0.000133) and South Asian in 2 of 28188 chromosomes (freq: 0.000071), while the variant was not observed in the Ashkenazi Jewish, East Asian or European (Finnish) populations. The p.Leu1201 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.
Clinical Genetics, Academic Medical Center	RCV000085583	SCV001925438	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000176456	SCV001951648	benign	not specified		no assertion criteria provided	clinical testing