ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.5917del (p.Gly1972_Val1973insTer)

dbSNP: rs61751389
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Total submissions: 20
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg RCV000408561 SCV000281942 pathogenic Severe early-childhood-onset retinal dystrophy 2016-01-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000085776 SCV001234634 pathogenic not provided 2023-12-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val1973*) 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 (rs61751389, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with Stargardt disease and inherited retinal disease (PMID: 28041643, 29099798). ClinVar contains an entry for this variant (Variation ID: 99419). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV000504777 SCV001238899 pathogenic Retinal dystrophy 2018-12-22 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000085776 SCV001247600 pathogenic not provided 2024-07-01 criteria provided, single submitter clinical testing ABCA4: PM3:Very Strong, PVS1, PM2
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000085776 SCV001446878 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Genomics England Pilot Project, Genomics England RCV001542556 SCV001760044 pathogenic Retinitis pigmentosa 19 criteria provided, single submitter clinical testing
DBGen Ocular Genomics RCV000408561 SCV001816100 pathogenic Severe early-childhood-onset retinal dystrophy 2021-05-31 criteria provided, single submitter clinical testing
Laboratory of Medical Genetics, National & Kapodistrian University of Athens RCV000408561 SCV001976839 pathogenic Severe early-childhood-onset retinal dystrophy 2021-10-05 criteria provided, single submitter clinical testing PVS1, PM2, PP5
Institute of Human Genetics, University Hospital Muenster RCV004584348 SCV002054120 pathogenic See cases 2023-04-20 criteria provided, single submitter clinical testing ACMG categories: PVS1,PM2,PM3,PP4,PP5
MGZ Medical Genetics Center RCV000408561 SCV002579837 pathogenic Severe early-childhood-onset retinal dystrophy 2021-12-03 criteria provided, single submitter clinical testing
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München RCV000408561 SCV004045888 pathogenic Severe early-childhood-onset retinal dystrophy 2023-01-25 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV003985075 SCV004801488 pathogenic ABCA4-related disorder 2020-05-13 criteria provided, single submitter clinical testing The ABCA4 c.5917delG p.(Val1973Ter) nonsense variant is expected to result in the loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Across a selection of the available literature, the c.5917delG p.(Val1973Ter) variant has been identified in a total of 15 individuals with ABCA4 -related disorders including in nine individuals diagnosed with Stargardt disease, in three of whom the variant was found in a homozygous state, and in six of whom, the variant was found in a compound heterozygous state. Of six individuals diagnosed with cone-rod dystrophy, four carried the variant in a homozygous state, and two in a presumed compound heterozygous state (Rivera et al. 2000; Biggs et al. 2001; Gerth et al. 2002; Riveiro-Alvarez et al. 2013; Schulz et al. 2017; Dockery et al. 2017; Weisschuh et al. 2018). This variant is reported at a frequency of 0.000163 in the South Asian population of the Genome Aggregation Database (version 2.1.1). This allele frequency is consistent with the disease prevalence estimates. Based on the collective evidence the c.5917delG p.(Val1973Ter) variant is classified as pathogenic for ABCA4 -related disorders.
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV000408561 SCV005086231 pathogenic Severe early-childhood-onset retinal dystrophy 2023-07-17 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Stargardt disease 1 (MIM#248200). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0115 - Variants in this gene are known to have variable expressivity (PMID: 31522899). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v2: 7 heterozygotes, 0 homozygotes). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (Clinvar, DECIPHER). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. It has been reported in at least ten Stargardt disease 1 (MIM#248200) patients and classified as pathogenic by diagnostic laboratories in ClinVar (PMID: 16303926, 24453473). (SP) 1206 - This variant has been shown to be paternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Neuberg Centre For Genomic Medicine, NCGM RCV000408561 SCV005382420 pathogenic Severe early-childhood-onset retinal dystrophy 2023-05-20 criteria provided, single submitter clinical testing The frameshift c.5917del (p.Val1973Ter) variant in the ABCA4 gene has been observed in individual(s) with Stargardt disease and inherited retinal disease (Carss, Keren J et al.,2017). This variant is reported with the allele frequency (0.002%) in the gnomAD Exomes. It is submitted to ClinVar as Pathogenic (multiple submissions). This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic.
Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel RCV000504777 SCV005415415 pathogenic Retinal dystrophy 2024-05-27 criteria provided, single submitter research
Retina International RCV000085776 SCV000117918 not provided not provided no assertion provided not provided
NIHR Bioresource Rare Diseases, University of Cambridge RCV000504777 SCV000599004 pathogenic Retinal dystrophy 2015-01-01 no assertion criteria provided research
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000678514 SCV000804585 pathogenic Age related macular degeneration 2 2016-09-01 no assertion criteria provided clinical testing
Sharon lab, Hadassah-Hebrew University Medical Center RCV001002810 SCV001160822 pathogenic maculopathy 2019-06-23 no assertion criteria provided research
Faculty of Health Sciences, Beirut Arab University RCV001257850 SCV001434617 pathogenic Autosomal recessive retinitis pigmentosa 2018-09-03 no assertion criteria provided literature only

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