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.884C>G (p.Ser295Ter)

CA229834

102884 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 6d125790-217d-4bb8-aeab-b6ee4f35be49

HGVS expressions

NM_000277.2:c.884C>G

NM_000277.2(PAH):c.884C>G (p.Ser295Ter)

NC_000012.12:g.102851715G>C

CM000674.2:g.102851715G>C

NC_000012.11:g.103245493G>C

CM000674.1:g.103245493G>C

NC_000012.10:g.101769623G>C

NG_008690.1:g.70888C>G

NG_008690.2:g.111696C>G

NM_000277.1:c.884C>G

NM_001354304.1:c.884C>G

NM_000277.3:c.884C>G

ENST00000307000.7:c.869C>G

ENST00000549247.6:n.643C>G

ENST00000551114.2:n.546C>G

ENST00000553106.5:c.884C>G

ENST00000635477.1:n.45C>G

Pathogenic

PVS1 PM2 PP4

PM3

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.884C>G (p.S295*) variant in PAH has been reported in 1 individual with PKU, however without indication of complete genotype (PMID:10394930). This variant is absent in population databases, including 1000 Genomes, Exome Sequencing Project (ESP) and the Genome Aggregation database (gnomAD). This is a nonsense variant in exon 8 of 13 in PAH, predicted to undergo nonsense mediated decay with the truncated region critical to protein function. Overall this variant meets criteria to be classified as pathogenic for PAH. ACMG/AMP criteria applied: PM2, PVS1, PP4.

PVS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PP4

Reported in a phenyketonuria cohort in an allele of Arabian origin.

Reported in a phenyketonuria cohort in an allele of Arabian origin. PubMed:10394930

PM3

Reported in a phenyketonuria cohort in an allele of Arabian origin. The genotype of the affected individual was not reported. PubMed:10394930

Approved on: 2019-07-14

Published on: 2019-07-14

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