ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.168+2T>C

dbSNP: rs1025860114
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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 RCV000993645 SCV001146777 pathogenic Phenylketonuria 2019-04-09 reviewed by expert panel curation The c.168+2T>C variant in PAH was reported in one patient with PKU (BH4 deficiency excluded) in trans with p.R243Q (PP4_Moderate, PM3; PMID: 28982351). This variant is absent from population databases, including gnomAD (PM2). This variant occurs at a canonical splice site, which will result in abnormal splicing at the donor site of intron 2 where LOF is a known mechanism of disease, exon skipping preserves reading frame, but the altered region is critical to protein function (14 non-truncating pathogenic variants in the region). (PVS1_strong). In summary, this variant meets the criteria to be classified pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PP4_Moderate, PVS1_strong, PM2, PM3.
Juno Genomics, Hangzhou Juno Genomics, Inc RCV000993645 SCV005417948 pathogenic Phenylketonuria criteria provided, single submitter clinical testing PVS1_Strong+PM2+PM3+PP4_Moderate

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