Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001387654 | SCV001588326 | pathogenic | not provided | 2024-02-02 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu210Argfs*31) 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 variant has not been reported in the literature in individuals affected with ABCA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1074381). For these reasons, this variant has been classified as Pathogenic. |
| Broad Center for Mendelian Genomics, |
RCV002551560 | SCV003761283 | likely pathogenic | ABCA4-related retinopathy | 2023-01-25 | criteria provided, single submitter | curation | The heterozygous p.Leu210ArgfsTer31 variant in ABCA4 was identified by our study, in the compound heterozygous state with a pathogenic variant (ClinVar Variation ID: 7882), in one individual with rod-cone dystrophy. This individual also carried a pathogenic variant (ClinVar Variation ID: 7882); however, the phase of these variants is unknown at this time. The p.Leu210ArgfsTer31 variant in ABCA4 has not been previously reported in individuals with autosomal recessive ABCA4-related retinopathy. This variant was absent from large population studies. This variant has also been reported in ClinVar (Variation ID: 1074381) and has been interpreted as pathogenic by Invitae. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 210 and leads to a premature termination codon 31 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the ABCA4 gene is an established disease mechanism in autosomal recessive ABCA4-related retinopathy. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal recessive ABCA4-related retinopathy. ACMG/AMP Criteria applied: PVS1, PM2_Supporting (Richards 2015). |