ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.1199+2T>G

dbSNP: rs62508737
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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 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

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