ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.887A>G (p.Asp296Gly) (rs281865446)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PAH Variant Curation Expert Panel RCV000106372 SCV001146748 uncertain significance Phenylketonuria 2019-07-14 reviewed by expert panel curation The c.887A>G (p.Asp296Gly) variant in PAH has been reported in a proband with classic PKU (PMID: 26666653; PP4). The proband was heterozygous for variant; it was found with the known pathogenic (per ClinGen PAH Working Group; see ClinVar variant ID 577, c.1222C > T (p.Arg408Trp) allele; however, although the paper did say that parental samples were collected in the study, it did not explicitly state whether the phase of the variants was confirmed via parental testing. Thus, PM3 is downgraded to supporting. The variant is predicted damaging by multiple lines of computational evidence (PP3). It is absent from ethnically diverse control databases (PM2). Another missense at the site, p.Asp296His, has been previously reported (BioPKU PAH0955) heterozygous in a Chinese proband with PKU; no further information appears to be provided in the manuscript or supplementary information regarding phenotype or second variant (PMID: 26503515). In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PP4, PM2, PM3_supporting, PP3.
Inserm U 954, Faculté de Médecine de Nancy RCV000106372 SCV000143872 probable-pathogenic Phenylketonuria no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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