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]
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  • See Evidence submitted by expert panel for details.

CA16020715

Gene: PAH
Condition: phenylketonuria
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 3e11f683-5644-4adc-bee9-7e4513f592af

HGVS expressions

NM_000277.1:c.30dup
NC_000012.12:g.102917101dup
CM000674.2:g.102917101dup
NC_000012.11:g.103310879dup
CM000674.1:g.103310879dup
NC_000012.10:g.101835009dup
NG_008690.1:g.5502dup
NG_008690.2:g.46310dup
NM_000277.2:c.30dup
NM_001354304.1:c.30dup
NM_000277.3:c.30dup
ENST00000307000.7:c.-118dup
ENST00000546844.1:c.30dup
ENST00000547319.1:n.341dup
ENST00000549111.5:n.126dup
ENST00000550978.6:n.14dup
ENST00000551337.5:c.30dup
ENST00000551988.5:n.119dup
ENST00000553106.5:c.30dup
ENST00000635500.1:n.29-4203dup

Pathogenic

Met criteria codes 4
PM3_Supporting PP4_Moderate PM2 PVS1

Evidence Links 2

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Phenylketonuria VCEP
The PAH: c.30_31insC 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 previously reported with the known pathogenic p.R243Q allele (PM3-supporting, no parental analysis reported) in 1 Chinese case with classic PKU (PMID: 26322415), as assessed by plasma Phe levels; BH4 deficiency was excluded by analysis of urinary pterins and dihydropteridine reductase activity in erythrocytes (PP4_Moderate). It is absent from control databases including ethnically matched individuals, including gnomAD/ExAC, 1000 Genomes, and ESP (PM2).
Met criteria codes
PM3_Supporting
The variant has been previously reported in trans with the known pathogenic p.R243Q allele (PM3) in 1 Chinese case with classic PKU (PMID: 26322415). Parental testing not reported.
The variant has been previously reported in trans with the known pathogenic p.R243Q allele (PM3) in 1 Chinese case with classic PKU (PMID: 26322415), as assessed by plasma Phe levels; BH4 deficiency was excluded by analysis of urinary pterins and dihydropteridine reductase activity in erythrocytes (PP4_Moderate). PubMed:26322415
PP4_Moderate
The variant has been previously reported in trans with the known pathogenic p.R243Q allele (PM3) in 1 Chinese case with classic PKU (PMID: 26322415), as assessed by plasma Phe levels; BH4 deficiency was excluded by analysis of urinary pterins and dihydropteridine reductase activity in erythrocytes (PP4_Moderate). It is also noted as occurring in 1 Chinese PKU case, without further information and/or patient identifier, in another publication (PMID: 26503515) including the same authors as in the other publication, published in the same year. Thus conservatively, counted as occurring in 1 proband.
It is also noted as occurring in 1 Chinese PKU case, without further information and/or patient identifier, in another publication (PMID: 26503515) including the same authors as in the other publication, published in the same year. Thus conservatively, counted as occurring in 1 proband. PubMed:26503515
The variant has been previously reported in trans with the known pathogenic p.R243Q allele (PM3) in 1 Chinese case with classic PKU (PMID: 26322415), as assessed by plasma Phe levels; BH4 deficiency was excluded by analysis of urinary pterins and dihydropteridine reductase activity in erythrocytes (PP4_Moderate). PubMed:26322415
PM2
It is absent from control databases including ethnically matched individuals, including gnomAD/ExAC, 1000 Genomes, and ESP (PM2).
PVS1
The PAH: c.30_31insC 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).
Approved on: 2019-08-11
Published on: 2019-08-11
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