ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.6449G>A (p.Cys2150Tyr)

gnomAD frequency: 0.00005  dbSNP: rs61751384
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg RCV000408531 SCV000281959 likely pathogenic Severe early-childhood-onset retinal dystrophy 2016-01-01 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000085823 SCV000706612 pathogenic not provided 2017-03-29 criteria provided, single submitter clinical testing
Invitae RCV000085823 SCV001227419 pathogenic not provided 2023-11-19 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 2150 of the ABCA4 protein (p.Cys2150Tyr). This variant is present in population databases (rs61751384, gnomAD 0.006%). This missense change has been observed in individual(s) with bullseye maculopathy (PMID: 15579991, 23755871, 24743636, 25283059, 28559085). 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: 99463). 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%. This variant disrupts the p.Cys2150 amino acid residue in ABCA4. Other variant(s) that disrupt this residue have been observed in individuals with ABCA4-related conditions (PMID: 11527935), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001074378 SCV001239956 pathogenic Retinal dystrophy 2019-07-30 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000085823 SCV001247595 pathogenic not provided 2019-07-01 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000085823 SCV001446805 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
GeneDx RCV000085823 SCV001827128 pathogenic not provided 2020-11-17 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32467599, 32581362, 28559085, 18977788, 29925512, 27820952, 19074458, 10206579, 25283059, 25342616, 11527935, 11673412, 14971589, 16917483, 10634594, 24677105, 26743751, 25139735, 23096905, 19243736, 15579991, 28118664, 24743636, 22264887, 25301883, 18024811, 15192030, 11702214, 11328725, 14517951)
Retina International RCV000085823 SCV000117966 not provided not provided no assertion provided not provided
NIHR Bioresource Rare Diseases, University of Cambridge RCV000408531 SCV000599018 likely pathogenic Severe early-childhood-onset retinal dystrophy 2015-01-01 no assertion criteria provided research

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