Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000673497 | SCV004015329 | likely pathogenic | Phenylketonuria | 2023-03-16 | reviewed by expert panel | curation | The c.1199+2T>G variant in PAH occurs within the canonical splice donor of intron 11. It is predicted to cause skipping of biologically-relevant exon 11, resulting in a frameshift leading to nonsense mediated decay in a gene in which loss of function is an established disease mechanism. This variant may be reported in the literature (PMID: 25863075), but is unavailable for evaluation. Sequence analysis of a PKU mouse model with this variant revealed two cryptic splice donor sites, upstream and downstream of the wild-type splice site (PMID: 11161825). This variant is absent in population databases. In summary, this variant meets criteria to be classified as Likely Pathogenic for PAH deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen PAH VCEP: PM2, PVS1 |
Counsyl | RCV000673497 | SCV000798705 | likely pathogenic | Phenylketonuria | 2018-03-20 | criteria provided, single submitter | clinical testing |