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_000277.3(PAH):c.970-2A>C

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA229882

102918 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 04a5baca-0358-4e19-80e9-b48e581d6e63

Approved on: 2020-08-27

Published on: 2020-08-27

HGVS expressions

NM_000277.3:c.970-2A>C

NM_000277.3(PAH):c.970-2A>C

NC_000012.12:g.102844433T>G

CM000674.2:g.102844433T>G

NC_000012.11:g.103238211T>G

CM000674.1:g.103238211T>G

NC_000012.10:g.101762341T>G

NG_008690.1:g.78170A>C

NG_008690.2:g.118978A>C

NM_000277.1:c.970-2A>C

NM_000277.2:c.970-2A>C

NM_001354304.1:c.970-2A>C

NM_001354304.2:c.970-2A>C

ENST00000307000.7:c.955-2A>C

ENST00000549247.6:n.729-2A>C

ENST00000551114.2:n.632-2A>C

ENST00000553106.5:c.970-2A>C

ENST00000635477.1:n.74-2A>C

ENST00000635528.1:n.485-2A>C

Likely Pathogenic

PM2 PP4 PM3_Supporting PVS1_Strong

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.970-2A>C variant in PAH is a canonical splice-site variant predicted to lead to skipping of exon 10 (PVS1_Strong). It is absent from ethnically diverse control databases, including gnomAD/ExAC, 1000 Genomes, and ESP (PM2). It is reported in ClinVar (variant ID 102918), without a classification. It has been previously reported (PMID: 7866411) in one Polish proband with classic PKU (as ascertained by abnormal blood Phe levels; BH4 deficiency does not appear to have been formally excluded) (PP4), who was homozygous for the variant (0.5 points; PM3_Supporting). Classification: Likely Pathogenic Supporting Criteria: PVS1_Strong; PM2; PM3_Supporting; PP4

PM2

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

PP4

It has been previously reported (PMID: 7866411) in one Polish proband with classic PKU (as ascertained by abnormal blood Phe levels; BH4 deficiency does not appear to have been formally excluded) (PP4), who was homozygous for the variant (0.5 points; PM3_Supporting).

PM3_Supporting

reported (PMID: 7866411) in one Polish proband who was homozygous for the variant. Haplotype analysis was performed (manually) for patients, and the methods were as in their prior publications (PMID: 1671770) where parental analysis is explicitly noted (0.5 points; PM3_Supporting).

PVS1_Strong

The c.970-2A>C variant in PAH is a canonical splice-site variant predicted to lead to skipping of exon 10 (PVS1_Strong).

Curation History

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