ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.214G>A (p.Gly72Arg) (rs61751412)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001000882 SCV001157964 likely pathogenic not specified 2019-01-03 criteria provided, single submitter clinical testing The ABCA4 c.214G>A; p.Gly72Arg variant (rs617514127) is published in the medical literature in individuals with Stargardt or ABCA4-related disease in the compound heterozygous or homozygous state (Birtel 2018, Garces 2018, Khan 2018, Rivera 2000, Rosenberg 2007). The variant is reported in the ClinVar database (Variation ID: 99120) and in the general population with an allele frequency of 0.003% (7/251414 alleles) in the Genome Aggregation Database. The glycine at this position is highly conserved and computational algorithms (PolyPhen-2, SIFT) predict this variant is deleterious. In support of this prediction, experiments show reduced binding and ATPase activity compared to the wild type protein (Garces 2018). Considering available evidence, this variant is classified as likely pathogenic. References: Birtel J et al. Clinical and genetic characteristics of 251 consecutive patients with macular and cone/cone-rod dystrophy. Sci Rep. 2018 Mar 19;8(1):4824. Garces F et al. Correlating the Expression and Functional Activity of ABCA4 Disease Variants With the Phenotype of Patients With Stargardt Disease. Invest Ophthalmol Vis Sci. 2018 May 1;59(6):2305-2315. Khan KN et al. Early Patterns of Macular Degeneration in ABCA4-Associated Retinopathy. Ophthalmology. 2018 May;125(5):735-746. Rivera A et al. A comprehensive survey of sequence variation in the ABCA4 (ABCR) gene in Stargardt disease and age-related macular degeneration. Am J Hum Genet. 2000 Oct;67(4):800-13. Rosenberg T et al. N965S is a common ABCA4 variant in Stargardt-related retinopathies in the Danish population. Mol Vis. 2007 Oct 17;13:1962-9.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000085464 SCV001247764 pathogenic not provided 2019-07-01 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000085464 SCV001446806 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Institute of Medical Molecular Genetics, University of Zurich RCV001353042 SCV001548161 likely pathogenic Stargardt disease 1 2021-01-30 criteria provided, single submitter clinical testing
Invitae RCV000085464 SCV001590830 pathogenic not provided 2020-10-19 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 72 of the ABCA4 protein (p.Gly72Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs61751412, ExAC 0.006%). This variant has been observed in individual(s) with inherited retinal disease (PMID: 30945053, 22264887, 30834176, 28355279). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 99120). This variant has been reported to affect ABCA4 protein function (PMID: 29847635). For these reasons, this variant has been classified as Pathogenic.
Retina International RCV000085464 SCV000117601 not provided not provided no assertion provided not provided
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000787776 SCV000926783 likely pathogenic Stargardt disease 2018-04-01 no assertion criteria provided research

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