Total submissions: 20
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics, |
RCV000408561 | SCV000281942 | pathogenic | Severe early-childhood-onset retinal dystrophy | 2016-01-01 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
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 | |
Ce |
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, |
RCV000085776 | SCV001446878 | pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
Genomics England Pilot Project, |
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, |
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, |
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, |
RCV000408561 | SCV004045888 | pathogenic | Severe early-childhood-onset retinal dystrophy | 2023-01-25 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
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, |
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, |
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, |
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, |
RCV000504777 | SCV000599004 | pathogenic | Retinal dystrophy | 2015-01-01 | no assertion criteria provided | research | |
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000678514 | SCV000804585 | pathogenic | Age related macular degeneration 2 | 2016-09-01 | no assertion criteria provided | clinical testing | |
Sharon lab, |
RCV001002810 | SCV001160822 | pathogenic | maculopathy | 2019-06-23 | no assertion criteria provided | research | |
Faculty of Health Sciences, |
RCV001257850 | SCV001434617 | pathogenic | Autosomal recessive retinitis pigmentosa | 2018-09-03 | no assertion criteria provided | literature only |