Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
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  • No CSPEC computed assertion could be determined for this classification!
  • See Evidence submitted by expert panel for details.

CA229518

102652 (ClinVar)

Gene: PAH
Condition: phenylketonuria
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 558984a6-51b6-4793-b0f2-86e7c5b8d83c
Approved on: 2022-10-14
Published on: 2022-10-14

HGVS expressions

NM_000277.3:c.344_347del
NC_000012.12:g.102894744_102894747del
CM000674.2:g.102894744_102894747del
NC_000012.11:g.103288522_103288525del
CM000674.1:g.103288522_103288525del
NC_000012.10:g.101812652_101812655del
NG_008690.1:g.27860_27863del
NG_008690.2:g.68668_68671del
ENST00000553106.6:c.344_347del
ENST00000307000.7:c.329_332del
ENST00000546844.1:c.344_347del
ENST00000548928.1:n.266_269del
ENST00000549111.5:n.440_443del
ENST00000550978.6:c.328_331del
ENST00000551337.5:c.344_347del
ENST00000551988.5:n.433_436del
ENST00000553106.5:c.344_347del
NM_000277.1:c.344_347del
NM_000277.2:c.344_347del
NM_001354304.1:c.344_347del
NM_001354304.2:c.344_347del
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Pathogenic

Met criteria codes 4
PP4 PM2 PM3_Supporting PVS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Phenylketonuria VCEP
This c.344_347del (p.Lys115fs) variant in PAH was detected with the c.1315+1G>A pathogenic variant and the c.1066-14C>G likely pathogenic variant in multiple patients with PKU, phasing was not available (PMID: 11207989, 28676969, 25551302). This variant was absent in population databases. This is a frameshift variant in exon 3 of 13 coding exons with termination at position 194 predicted to undergo nonsense mediated decay. In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PM3_Supporting, PP4.
Met criteria codes
PP4
Variant was detected in multiple patients with PKU. PMID: 11207989, 28676969, 25551302.
PM2
This variant is absent from population databases gnomAD and ExAC
PM3_Supporting
This variant was detected with the c.1315+1G>A pathogenic variant (no phasing available) PMID: 25551302. It was detected with the likely pathogenic variant c.1066-14C>G. PMID: 11207989. points=0.75.
PVS1
Frameshift variant predicted to undergo NMD. Termination occurs at position 194 (115+79). Located in exon 3 out of 13 coding exons, not in the last 50bp of exon 12.
Curation History
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