ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.5312+3A>T

dbSNP: rs767451031
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000779000 SCV000915441 uncertain significance ABCA4-related disorder 2017-10-18 criteria provided, single submitter clinical testing The ABCA4 c.5312+3A>T variant has been reported in one study in which it was found in a compound heterozygous state with a second null variant in two siblings diagnosed with an uncommon phenotype of juveline Stargardt disease that rapidly progressed to severe cone-rod dystrophy. The c.5312+3A>T variant co-segregated with disease in this family and was absent from 200 controls (Xi et al. 2009). This variant is not found in the 1000 Genomes Project, the Exome Sequencing Project, the Exome Aggregation Consortium, or the Genome Aggregation Database in a region with good sequence coverage. Hence, the variant is presumed to be rare. The evidence for this variant is limited. The c.5312+3A>T variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for ABCA4-related disorders.
Labcorp Genetics (formerly Invitae), Labcorp RCV001869142 SCV002247410 pathogenic not provided 2023-10-03 criteria provided, single submitter clinical testing This sequence change falls in intron 37 of the ABCA4 gene. It does not directly change the encoded amino acid sequence of the ABCA4 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with Stargardt disease (PMID: 19352439). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 632118). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 29162642). For these reasons, this variant has been classified as Pathogenic.

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