ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.6118C>T (p.Arg2040Ter)

gnomAD frequency: 0.00001  dbSNP: rs61753038
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000085790 SCV000344007 pathogenic not provided 2016-08-16 criteria provided, single submitter clinical testing
GeneDx RCV000085790 SCV000890157 pathogenic not provided 2018-10-24 criteria provided, single submitter clinical testing The R2040X nonsense variant in the ABCA4 gene has been reported in association with Stargardt disease (Baum et al., 2003; Downes et al., 2012; Fujinami et al., 2013; Jiang et al., 2016). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R2040X variant was observed in 3/18866 (0.016%) alleles in East Asian individuals in large population databases (Lek et al., 2016). We interpret R2040X as a pathogenic variant.
Fulgent Genetics, Fulgent Genetics RCV000763435 SCV000894202 pathogenic Cone-rod dystrophy 3; Age related macular degeneration 2; Severe early-childhood-onset retinal dystrophy; Retinitis pigmentosa 19 2018-10-31 criteria provided, single submitter clinical testing
Blueprint Genetics RCV001073783 SCV001239344 pathogenic Retinal dystrophy 2018-01-15 criteria provided, single submitter clinical testing
Invitae RCV000085790 SCV001412233 pathogenic not provided 2023-10-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg2040*) in the ABCA4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCA4 are known to be pathogenic (PMID: 10958761, 24938718, 25312043, 26780318). This variant is present in population databases (rs61753038, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with ABCA4-related retinal dystrophy (PMID: 26161775, 29555955, 29925512; Invitae). ClinVar contains an entry for this variant (Variation ID: 99431). For these reasons, this variant has been classified as Pathogenic.
3billion RCV002283455 SCV002572603 pathogenic Severe early-childhood-onset retinal dystrophy 2022-09-01 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: 0.001%). Stop-gained (nonsense) is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000099431 / PMID: 12592048 / 3billion dataset). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
Retina International RCV000085790 SCV000117932 not provided not provided no assertion provided not provided
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet RCV000787772 SCV000926777 likely pathogenic Stargardt disease 2018-04-01 no assertion criteria provided research

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