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]

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Variant: NM_000277.2(PAH):c.547_548delGAinsTT (p.Glu183Leu)

CA267658

120278 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 3e905683-806d-4709-8aaf-b71562b3bf03

Approved on: 2019-08-11

Published on: 2019-08-11

HGVS expressions

NM_000277.2:c.547_548delGAinsTT

NM_000277.2(PAH):c.547_548delGAinsTT (p.Glu183Leu)

NM_000277.1:c.547_548delinsTT

NM_000277.2:c.547_548delinsTT

NM_001354304.1:c.547_548delinsTT

NM_000277.3:c.547_548delinsTT

ENST00000307000.7:c.532_533delinsTT

ENST00000549111.5:n.643_644delinsTT

ENST00000551988.5:n.568_569delinsTT

ENST00000553106.5:c.547_548delinsTT

NC_000012.12:g.102855294_102855295delinsAA

CM000674.2:g.102855294_102855295delinsAA

NC_000012.11:g.103249072_103249073delinsAA

CM000674.1:g.103249072_103249073delinsAA

NC_000012.10:g.101773202_101773203delinsAA

NG_008690.1:g.67308_67309delinsTT

NG_008690.2:g.108116_108117delinsTT

Likely Pathogenic

PM3 PM2 PP4 PP3

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.547_548delGAinsTT PAH variant has been identified in at least one patient with classic PKU (PMID: 26666653). It was detected in trans with the pathogenic variant c.143T>C; p.Leu48Ser (ClinVar 608). This variant is absent from 1000G, ESP, and gnomAD databases. It is predicted deleterious in multiple in silico models. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PP4, PM2, PM3, PP3.

PM3

This variant has been observed in trans with the previously assessed pathogenic variant c.143T>C; p.Leu48Ser (ClinVar 608, Pathogenic).

This variant has been observed in trans with the previously assessed pathogenic variant c.143T>C; p.Leu48Ser (ClinVar 608, Pathogenic). PubMed:26666653

PM2

The variant is absent from ExAC, gnomAD, 1000G, and ESP.

PP4

A compound heterozygous proband with this variant was described with the classic PKU phenotype and PHE >1200umol/L. Defects in BH4 cofactor metabolism were not excluded.

A compound heterozygous proband with this variant was described with the classic PKU phenotype and PHE >1200umol/L. Defects in BH4 cofactor metabolism were not excluded. PubMed:26666653

PP3

MutationTaster: Disease Causing; PolyPhen-2: Probably Damaging; PROVEAN: Deleterious; SIFT: Damaging

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