ClinVar Miner

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

gnomAD frequency: 0.00001  dbSNP: rs1005271380
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001059911 SCV001224565 pathogenic not provided 2024-01-04 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

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.