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]

Variant: NM_000277.1(PAH):c.266dupC (p.Ala90Cysfs)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA229503

102642 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 576bbc2e-c3f8-4d05-8b80-899d55eae361

Approved on: 2020-05-08

Published on: 2020-05-08

HGVS expressions

NM_000277.1:c.266_267insC

NM_000277.1:c.266dupC

NM_000277.1:c.264_265insC

NM_000277.1(PAH):c.266dupC (p.Ala90Cysfs)

NC_000012.12:g.102894822dup

CM000674.2:g.102894822dup

NC_000012.11:g.103288600dup

CM000674.1:g.103288600dup

NC_000012.10:g.101812730dup

NG_008690.1:g.27782dup

NG_008690.2:g.68590dup

NM_000277.1:c.266dup

NM_000277.2:c.266dup

NM_001354304.1:c.266dup

NM_000277.3:c.266dup

NM_001354304.2:c.266dup

ENST00000307000.7:c.251dup

ENST00000546844.1:c.266dup

ENST00000548677.2:n.353dup

ENST00000548928.1:n.188dup

ENST00000549111.5:n.362dup

ENST00000550978.6:n.250dup

ENST00000551337.5:c.266dup

ENST00000551988.5:n.355dup

ENST00000553106.5:c.266dup

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

Variant classified as Pathogenic using the following criteria: PVS1; PM2; PM3; PP4_Moderate. PVS1: frameshift variant in exon 2 of 13, predicted to result in PTC with removal of >10% of the protein and NMD; PM2: absent from ExAC, gnomAD, 1000G, ESP. PP4_Moderate; PM3: c.266_267insC seen on 2 PKU alleles, with BH4 deficiency ruled out (PMID: 21147011). Detected with pathogenic variants IVS12+1G>A and p.I65T (PMID: 9452062); and p.Pro281Leu (Likely Pathogenic per ClinGen PAH VCEP, PMID: 26666653).

PVS1

PVS1: frameshift variant in exon 2 of 13, predicted to result in PTC with removal of >10% of the protein and NMD

PM3

found in with IVS12+1G>A (Pathogenic per ClinGen PAH VCEP) and p.I65T (P 10 submitters) parental analysis not reported (PMID: 9452062); with p.Pro281Leu (Likely Pathogenic per ClinGen PAH VCEP) in one French PKU case parental analysis not reported (PMID: 26666653). p.P281R in 2 patients, parental analysis not reported PMID: 21147011

PubMed:21147011

PM2

absent from ExAC, gnomAD, 1000G, ESP

PP4_Moderate

c.266_267insC seen on 2 PKU alleles. BH4 deficiency ruled out. Upgraded per ClinGen Metabolic workgroup

588 hyperphenylalaninemic patients were investigated. Assessment included PAH gene and genes of the BH4 synthesis/recycling pathways (PTS and QDPR). c.266_267insC seen in 2 alleles. PubMed:21147011

Curation History

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.