Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000192386 | SCV000248574 | pathogenic | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3 | 2015-06-08 | criteria provided, single submitter | clinical testing | |
Broad Center for Mendelian Genomics, |
RCV002517120 | SCV003761165 | uncertain significance | Muscular dystrophy-dystroglycanopathy | 2023-01-24 | criteria provided, single submitter | curation | The c.1413+1G>C variant in POMGNT1 has not been previously reported in the literature in individuals with POMGNT1-associated muscular dystrophy-dystroglycanopathy but has been identified in 0.01% (3/30616) of South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs587777821). 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 (Variation ID#:211939) and has been interpreted as pathogenic by the University of Chicago Genetic Services Library. This variant is located in the 5' 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. Loss of function of the POMGNT1 gene is an established disease mechanism in autosomal recessive POMGNT1-associated muscular dystrophy-dystroglycanopathy. In summary, the clinical significance of the c.1413+1G>C variant is uncertain. ACMG/AMP Criteria applied: PVS1_Moderate, PM2_Supporting (Richards 2015). |