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_000277.1(PAH):c.111_112insG (p.Ile38Aspfs)

CA229354

102531 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: b99c1dbd-f61d-48b6-b621-b15e0731824b

HGVS expressions

NM_000277.1:c.111_112insG

NM_000277.1(PAH):c.111_112insG (p.Ile38Aspfs)

NM_000277.1:c.111dup

NM_000277.2:c.111dup

NM_001354304.1:c.111dup

NM_000277.3:c.111dup

ENST00000307000.7:c.96dup

ENST00000546844.1:c.111dup

ENST00000548677.2:n.198dup

ENST00000548928.1:n.33dup

ENST00000549111.5:n.207dup

ENST00000550978.6:n.95dup

ENST00000551337.5:c.111dup

ENST00000551988.5:n.200dup

ENST00000553106.5:c.111dup

ENST00000635500.1:n.79dup

NC_000012.12:g.102912848dup

CM000674.2:g.102912848dup

NC_000012.11:g.103306626dup

CM000674.1:g.103306626dup

NC_000012.10:g.101830756dup

NG_008690.1:g.9755dup

NG_008690.2:g.50563dup

Pathogenic

PVS1 PP4 PM2

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.112dupG variant in PAH has been previously reported as a single variant (no second mutation detected) in 1 Chinese patient with classic PKU (PMID: 16256386); BH4 deficiency was not excluded (PP4). The variant is a frameshift variant occurring in exon 2 of 13 in the in the canonical transcript of PAH, a gene fulfilling the most recent criteria for LOF being a known disease mechanism (see PMID: 30192042) (PVS1). It is absent from control databases including ethnically matched individuals, including gnomAD/ExAC, 1000 Genomes, and ESP (PM2). In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PP4, PM2.

PVS1

The variant is a frameshift variant occurring in exon 2 of 13 in the 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 c.112dupG variant in PAH has been previously reported as a single variant (no second mutation detected) in 1 Chinese case with classic PKU (PMID: 16256386); BH4 deficiency was not excluded (PP4). It has also been noted in ClinVar (Variant ID 108267), without further information, and no assertion is provided re its classification.

PM2

It is absent from control databases including ethnically matched individuals, including gnomAD/ExAC, 1000 Genomes, and ESP (PM2).

Approved on: 2019-04-03

Published on: 2019-08-16

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.