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_000277.2(PAH):c.884C>G (p.Ser295Ter)

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Curation History
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CA229834

102884 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

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

Approved on: 2019-07-14

Published on: 2019-07-14

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 PP4 PM2

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

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

PM2

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

PM3

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

Curation History

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