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NM_000277.3(PAH):c.510-2A>G

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Interpretation:
Pathogenic​

Review status:
reviewed by expert panel FDA Recognized Database
Submissions:
3 (Most recent: Dec 3, 2020)
Last evaluated:
Oct 28, 2020
Accession:
VCV000551658.3
Variation ID:
551658
Description:
single nucleotide variant
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NM_000277.3(PAH):c.510-2A>G

Allele ID
546619
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
12q23.2
Genomic location
12: 102855334 (GRCh38) GRCh38 UCSC
12: 103249112 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000012.11:g.103249112T>C
NC_000012.12:g.102855334T>C
NM_000277.3:c.510-2A>G MANE Select splice acceptor
... more HGVS
Protein change
-
Other names
-
Canonical SPDI
NC_000012.12:102855333:T:C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
dbSNP: rs1555204750
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 3 reviewed by expert panel Oct 28, 2020 RCV000666780.3
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
PAH - - GRCh38
GRCh37
1103 1132

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Oct 28, 2020)
reviewed by expert panel
Method: curation
Phenylketonuria
(Autosomal recessive inheritance)
Allele origin: germline
ClinGen PAH Variant Curation Expert Panel
FDA Recognized Database
Accession: SCV001448248.1
Submitted: (Dec 03, 2020)
Evidence details
Publications
PubMed (3)
Other databases
https://erepo.clinicalgenome.org…
Comment:
This c.510-2A>G (aka IVS5-2A>G) variant in PAH has been observed in at least one patient with PAH deficiency; BH4 deficiency was ruled out (PMID: 26503515, … (more)
Likely pathogenic
(May 03, 2017)
criteria provided, single submitter
Method: clinical testing
Phenylketonuria
Allele origin: unknown
Counsyl
Accession: SCV000791134.1
Submitted: (Jul 10, 2018)
Evidence details
Publications
PubMed (2)
Likely pathogenic
(Oct 05, 2018)
criteria provided, single submitter
Method: clinical testing
Phenylketonuria
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000919921.1
Submitted: (Apr 24, 2019)
Evidence details
Publications
PubMed (2)
Comment:
Variant summary: PAH c.510-2A>G is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to … (more)

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
The Predictive Value of Genetic Analyses in the Diagnosis of Tetrahydrobiopterin (BH4)-Responsiveness in Chinese Phenylalanine Hydroxylase Deficiency Patients. Zhu T Scientific reports 2017 PMID: 28754886
Molecular characterisation of phenylketonuria in a Chinese mainland population using next-generation sequencing. Li N Scientific reports 2015 PMID: 26503515
Variations in genotype-phenotype correlations in phenylalanine hydroxylase deficiency in Chinese Han population. Zhu T Gene 2013 PMID: 23932990
Mutational spectrum of phenylketonuria in the Chinese Han population: a novel insight into the geographic distribution of the common mutations. Zhu T Pediatric research 2010 PMID: 19915519
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/66258a7c-6bc3-4f8b-bcbb-07ebbb24b5b4 - - - -

Text-mined citations for rs1555204750...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Aug 07, 2021