ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.6113G>A (p.Arg2038Gln)

gnomAD frequency: 0.00002  dbSNP: rs767729255
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000291561 SCV001545595 pathogenic not provided 2023-10-15 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 2038 of the ABCA4 protein (p.Arg2038Gln). This variant is present in population databases (rs767729255, gnomAD 0.006%). This missense change has been observed in individual(s) with retinitis pigmentosa and/or Stargardt disease (PMID: 33261146). 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: 282260). 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. This variant disrupts the p.Arg2038 amino acid residue in ABCA4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15161829, 24763286, 29854428, 29925512). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
3billion RCV002250614 SCV002521356 likely 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: 0.002%). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.89; 3Cnet: 0.85). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with ABCA4 related disorder (PMID: 33261146). A different missense change at the same codon (p.Arg2038Trp) has been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000099430). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.
Eurofins Ntd Llc (ga) RCV000291561 SCV000333627 uncertain significance not provided 2015-08-11 flagged submission clinical testing

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