ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.6316C>T (p.Arg2106Cys)

gnomAD frequency: 0.00034  dbSNP: rs61750648
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg RCV000408484 SCV000281955 likely pathogenic Severe early-childhood-onset retinal dystrophy 2016-01-01 criteria provided, single submitter clinical testing
GeneDx RCV000085806 SCV000490384 pathogenic not provided 2021-11-19 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 11379881, 9054934, 23143460, 25066811, 28044389, 28355279, 25283059, 30903310, 34426522, 31589614, 29114839, 32619608)
Blueprint Genetics RCV001075529 SCV001241155 pathogenic Retinal dystrophy 2018-12-04 criteria provided, single submitter clinical testing
Invitae RCV000085806 SCV001408471 pathogenic not provided 2024-01-31 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 2106 of the ABCA4 protein (p.Arg2106Cys). This variant is present in population databases (rs61750648, gnomAD 0.08%). This missense change has been observed in individual(s) with Stargardt disease (PMID: 11379881, 23143460, 25283059, 28355279). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 99447). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ABCA4 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects ABCA4 function (PMID: 11017087). This variant disrupts the p.Arg2106 amino acid residue in ABCA4. Other variant(s) that disrupt this residue have been observed in individuals with ABCA4-related conditions (PMID: 26161775, 28327576), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV000085806 SCV002018114 pathogenic not provided 2019-10-31 criteria provided, single submitter clinical testing
MGZ Medical Genetics Center RCV000408484 SCV002580593 likely pathogenic Severe early-childhood-onset retinal dystrophy 2021-12-20 criteria provided, single submitter clinical testing
Dept Of Ophthalmology, Nagoya University RCV001075529 SCV004705696 likely pathogenic Retinal dystrophy 2023-10-01 criteria provided, single submitter research
Retina International RCV000085806 SCV000117949 not provided not provided no assertion provided not provided

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