Evidence Repository - Clinical Genome Resources

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

Variant: NM_000277.2(PAH):c.1199+1G>C

CA274088

102557 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 97e81c3d-c06f-476a-b576-a37317f3f512

HGVS expressions

NM_000277.2:c.1199+1G>C

NM_000277.2(PAH):c.1199+1G>C

NC_000012.12:g.102843645C>G

CM000674.2:g.102843645C>G

NC_000012.11:g.103237423C>G

CM000674.1:g.103237423C>G

NC_000012.10:g.101761553C>G

NG_008690.1:g.78958G>C

NG_008690.2:g.119766G>C

NM_000277.1:c.1199+1G>C

NM_001354304.1:c.1199+1G>C

NM_000277.3:c.1199+1G>C

ENST00000307000.7:c.1184+1G>C

ENST00000549247.6:n.958+1G>C

ENST00000551114.2:n.861+1G>C

ENST00000553106.5:c.1199+1G>C

ENST00000635477.1:n.303+1G>C

ENST00000635528.1:n.714+1G>C

Pathogenic

PVS1 PM3 PM2 PP4_Moderate

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

PAH-specific ACMG/AMP criteria applied: PM2: 8.1e-6 allele frequency in GnomAD, not found in any other databases; PM3: [c.898G>T];[c.1199+1G>C] in a patient with mild hyperphe (180umol/L); PP4_Moderate: Single patient in Sterl 2013, BH4 defect excluded. Also identified in multiple other patients (7 publications linked through ClinVar) (PMID:22526846); PVS1: +1 canonical splice site. In summary this variant meets criteria to be classified as pathogenic for phenylketonuria in an autosomal recessive manner based on the ACMG/AMP criteria applied as specified by the PAH Expert Panel: (PM2, PM3, PP4_Moderate, PVS1).

PVS1

+1 canonical splice site

PM3

[c.898G>T];[c.1199+1G>C] in a patient with mild hyperphe (180umol/L)

PM2

8.1e-6 allele frequency in GnomAD, not found in any other databases

PP4_Moderate

Single patient in Sterl 2013, BH4 defect excluded. Also identified in multiple other patients (7 publications linked through ClinVar)

BH4 defect excluded in all patients PubMed:22526846

Approved on: 2018-08-27

Published on: 2019-08-17

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