ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.247_250dup (p.Ser84fs)

gnomAD frequency: 0.00001  dbSNP: rs1005271380
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001059911 SCV001224565 pathogenic not provided 2024-03-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser84Thrfs*16) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with Stargardt disease (PMID: 10711710, 25283059; Invitae). This variant is also known as 250insCAAA. ClinVar contains an entry for this variant (Variation ID: 854791). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001074519 SCV001240108 pathogenic Retinal dystrophy 2017-12-14 criteria provided, single submitter clinical testing
Institute of Medical Molecular Genetics, University of Zurich RCV001352948 SCV001548016 likely pathogenic Severe early-childhood-onset retinal dystrophy 2021-01-30 criteria provided, single submitter clinical testing
GeneDx RCV001059911 SCV002520293 pathogenic not provided 2022-05-12 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 15942264, 25283059, 11527935, 15192030, 20128570, 18652558, 21911583, 22661472, 24677105, 25342616, 28044389, 33369172, 33546218, 32037395, 29701254, 19265867, 10711710, 25097154)
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV002471023 SCV002767673 pathogenic Cone-rod dystrophy 3 2020-05-25 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as pathogenic. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0106 - This gene is known to be associated with autosomal recessive disease. (N) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein. (P) 0251 - Variant is heterozygous. (N) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (1 heterozygote, 0 homozygote). (P) 0701 - Comparable variants also predicted to cause NMD, have very strong previous evidence for pathogenicity (Decipher, ClinVar). (P) 0802 - Moderate previous evidence of pathogenicity in several unrelated individuals with Stargardt disease (ClinVar, LOVD, PMID:28044389, PMID:29178665, PMID: 28446513), (P) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign

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