Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000993636 | SCV001146768 | pathogenic | Phenylketonuria | 2019-07-15 | reviewed by expert panel | curation | The c.707-2delA variant in PAH has been reported in one patient, who carried a second pathogenic missense variant (p.Pro281Leu; BH4 deficiency not ruled out) (PMID: 19292873). The pre-treatment serum phenylalanine was reported at > 1500 micromolar. This variant is absent from gnomAD and ESP population databases, and disrupts the canonical splice acceptor site of intron 6, resulting in a frameshift and truncated protein (PMID: 19292873). Overall, the c.707-2delA variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM3, PVS1, PP4. |