Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000410235 | SCV000486250 | likely pathogenic | Hyperinsulinemic hypoglycemia, familial, 1 | 2016-05-03 | criteria provided, single submitter | clinical testing | |
Broad Center for Mendelian Genomics, |
RCV000410235 | SCV004026598 | uncertain significance | Hyperinsulinemic hypoglycemia, familial, 1 | 2023-08-16 | criteria provided, single submitter | curation | The c.2556+1G>A variant in ABCC8 has not been previously reported in the literature in individuals with hyperinsulinemic hypoglycemia, but has been identified in 0.002% (2/110648) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs749271190). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (VariationID: 370836) and has been interpreted as likely pathogenic by Counsyl. This variant is located in the 3' splice region. Computational tools predict a splicing impact, though this information is not predictive enough to determine pathogenicity. This variant is adjacent to an in-frame exon and is more likely to escape nonsense mediated decay (NMD) and result in a truncated protein. In summary, the clinical significance of the c.2556+1G>A variant is uncertain. ACMG/AMP Criteria applied: PVS1_moderate, PM2_supporting (Richards 2015). |