Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
Link to SEPIO compliant JSON-LD document
  • See Evidence submitted by expert panel for details.

CA16020716

Gene: PAH
Condition: phenylketonuria
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: c04f2ecf-3dc6-4936-9b14-dcfd8523534b

HGVS expressions

NM_000277.1:c.43_44insAG
NC_000012.12:g.102917087_102917088insCT
CM000674.2:g.102917087_102917088insCT
NC_000012.11:g.103310865_103310866insCT
CM000674.1:g.103310865_103310866insCT
NC_000012.10:g.101834995_101834996insCT
NG_008690.1:g.5515_5516insAG
NG_008690.2:g.46323_46324insAG
NM_000277.2:c.43_44insAG
NM_001354304.1:c.43_44insAG
NM_000277.3:c.43_44insAG
ENST00000307000.7:c.-105_-104insAG
ENST00000546844.1:c.43_44insAG
ENST00000547319.1:n.354_355insAG
ENST00000549111.5:n.139_140insAG
ENST00000550978.6:n.27_28insAG
ENST00000551337.5:c.43_44insAG
ENST00000551988.5:n.132_133insAG
ENST00000553106.5:c.43_44insAG
ENST00000635500.1:n.29-4190_29-4189insAG

Pathogenic

Met criteria codes 3
PM2 PVS1 PP4
Not Met criteria codes 1
PM3

Evidence Links 1

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Phenylketonuria VCEP
The PAH: c.43_44insAG variant is a frameshift variant occurring in exon 1 of 13 in the canonical transcript of PAH, a gene fulfilling the most recent criteria for LOF being a known disease mechanism (see PMID: 30192042) (PVS1). The variant has been reported with the IVS8-2A>G (c.913-2A>G) splice-site variant (PMID: 22513348), a recurrent splice-site variant among Central European PKU cases (see PMID: 23160875) in one Slovenian proband with classic PKU as assessed by plasma Phe levels; BH4 deficiency does not appear to have been formally excluded by biochemical or genetic testing (PP4). It is absent from control databases including ethnically matched individuals, including gnomAD/ExAC, 1000 Genomes, and ESP (PM2).
Met criteria codes
PM2
The variant is absent from control databases including ethnically matched individuals, including gnomAD/ExAC, 1000 Genomes, and ESP (PM2).
PVS1
The PAH: c.43_44insAG variant is a frameshift variant occurring in exon 1 of 13 in the canonical transcript of PAH, a gene fulfilling the most recent criteria for LOF being a known disease mechanism (see PMID: 30192042) (PVS1).
PP4
The variant has been previously reported in trans with the IVS8-2A>G (c.913-2A>G) splice-site variant (PMID: 22513348), a recurrent splice-site variant among Central European PKU cases (see PMID: 23160875) (PM3) in one Slovenian proband with classic PKU as assessed by plasma Phe levels; BH4 deficiency does not appear to have been formally excluded by biochemical or genetic testing (PP4).
The variant has been previously reported in trans with the IVS8-2A>G (c.913-2A>G) splice-site variant (PMID: 22513348), a recurrent splice-site variant among Central European PKU cases (see PMID: 23160875) (PM3) in one Slovenian proband with classic PKU as assessed by plasma Phe levels; BH4 deficiency does not appear to have been formally excluded by biochemical or genetic testing (PP4). PubMed:22513348
Not Met criteria codes
PM3
The variant has been reported with the IVS8-2A>G (c.913-2A>G) splice-site variant (PMID: 22513348), a recurrent splice-site variant among Central European PKU cases (see PMID: 23160875) (PM3-supporting) in one Slovenian proband.
The variant has been previously reported in trans with the IVS8-2A>G (c.913-2A>G) splice-site variant (PMID: 22513348), a recurrent splice-site variant among Central European PKU cases (see PMID: 23160875) (PM3) in one Slovenian proband with classic PKU as assessed by plasma Phe levels; BH4 deficiency does not appear to have been formally excluded by biochemical or genetic testing (PP4). PubMed:22513348
Approved on: 2019-08-12
Published on: 2019-08-12
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.