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NM_000277.3(PAH):c.47_48del (p.Leu15_Ser16insTer)

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Interpretation:
Pathogenic​

Review status:
reviewed by expert panel FDA Recognized Database
Submissions:
7 (Most recent: Dec 28, 2020)
Last evaluated:
Aug 10, 2018
Accession:
VCV000102696.4
Variation ID:
102696
Description:
2bp microsatellite
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NM_000277.3(PAH):c.47_48del (p.Leu15_Ser16insTer)

Allele ID
108432
Variant type
Microsatellite
Variant length
2 bp
Cytogenetic location
12q23.2
Genomic location
12: 102917083-102917084 (GRCh38) GRCh38 UCSC
12: 103310861-103310862 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000012.11:g.103310861AG[2]
NC_000012.12:g.102917083AG[2]
NM_000277.3:c.47_48del MANE Select NP_000268.1:p.Leu15_Ser16insTer nonsense
... more HGVS
Protein change
-
Other names
NM_000277.2(PAH):c.47_48delCT
Canonical SPDI
NC_000012.12:102917082:AGAGAG:AGAG
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA229574
dbSNP: rs62642906
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 5 reviewed by expert panel Aug 10, 2018 RCV000153638.12
Pathogenic 2 criteria provided, single submitter Apr 2, 2014 RCV000088944.2
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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
(Aug 10, 2018)
reviewed by expert panel
Method: curation
Phenylketonuria
(Autosomal recessive inheritance)
Allele origin: germline
ClinGen PAH Variant Curation Expert Panel
FDA Recognized Database
Accession: SCV000852108.3
Submitted: (Feb 25, 2019)
Evidence details
Publications
PubMed (1)
Other databases
https://erepo.clinicalgenome.org…
Comment:
PAH-specific ACMG/AMP criteria applied: PM2: ExAC:8.238e-06; gnomAD:0.000004062; 1000G + ESP: absent; PVS1: Null variant- frameshift. Subject to nonsense mediated decay.; PM3: found in trans with … (more)
Likely pathogenic
(Jan 26, 2015)
criteria provided, single submitter
Method: literature only
Phenylketonuria
(Autosomal recessive inheritance)
Allele origin: unknown
Counsyl
Accession: SCV000221085.1
Submitted: (Mar 11, 2015)
Evidence details
Publications
PubMed (11)
Pathogenic
(Sep 30, 2017)
criteria provided, single submitter
Method: clinical testing
Phenylketonuria
Allele origin: germline
Invitae
Accession: SCV000754077.1
Submitted: (Apr 02, 2018)
Evidence details
Publications
PubMed (2)
Comment:
This sequence change creates a premature translational stop signal (p.Ser16*) in the PAH gene. It is expected to result in an absent or disrupted protein … (more)
Pathogenic
(Apr 02, 2014)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000203188.7
Submitted: (Sep 19, 2018)
Evidence details
Publications
PubMed (1)
Other databases
http://www.egl-eurofins.com/emvc…
Pathogenic
(Mar 25, 2019)
criteria provided, single submitter
Method: clinical testing
Phenylketonuria
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001362289.1
Submitted: (Mar 06, 2020)
Evidence details
Publications
PubMed (4)
Comment:
Variant summary: PAH c.47_48delCT (p.Ser16X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Pathogenic
(Sep 16, 2020)
no assertion criteria provided
Method: clinical testing
Phenylketonuria
Allele origin: germline
Natera, Inc.
Accession: SCV001459232.1
Submitted: (Dec 28, 2020)
Evidence details
not provided
(-)
no assertion provided
Method: not provided
not provided
Allele origin: not provided
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE
Accession: SCV000119545.1
Submitted: (Mar 30, 2012)
Evidence details

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
Mutation analysis of the phenylalanine hydroxylase gene and prenatal diagnosis of phenylketonuria in Shaanxi, China. Wang L Journal of pediatric endocrinology & metabolism : JPEM 2017 PMID: 29176022
Correlation between genotype and the tetrahydrobiopterin-responsive phenotype in Chinese patients with phenylketonuria. Tao J Pediatric research 2015 PMID: 26322415
Phenylalanine hydroxylase deficiency in south Italy: Genotype-phenotype correlations, identification of a novel mutant PAH allele and prediction of BH4 responsiveness. Trunzo R Clinica chimica acta; international journal of clinical chemistry 2015 PMID: 26210745
Molecular Genetics and Genotype-Based Estimation of BH4-Responsiveness in Serbian PKU Patients: Spotlight on Phenotypic Implications of p.L48S. Djordjevic M JIMD reports 2013 PMID: 23430547
Hyperphenylalaninemia in the Czech Republic: genotype-phenotype correlations and in silico analysis of novel missense mutations. Réblová K Clinica chimica acta; international journal of clinical chemistry 2013 PMID: 23357515
Molecular genetics and impact of residual in vitro phenylalanine hydroxylase activity on tetrahydrobiopterin responsiveness in Turkish PKU population. Dobrowolski SF Molecular genetics and metabolism 2011 PMID: 21147011
A limited spectrum of phenylalanine hydroxylase mutations is observed in phenylketonuria patients in western Poland and implications for treatment with 6R tetrahydrobiopterin. Dobrowolski SF Journal of human genetics 2009 PMID: 19444284
Predicting a clinical/biochemical phenotype for PKU/MHP patients with PAH gene mutations. Kasnauskiene J Genetika 2008 PMID: 19062537
Molecular genetics of tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency. Zurflüh MR Human mutation 2008 PMID: 17935162
Molecular and phenotypic characteristics of patients with phenylketonuria in Serbia and Montenegro. Stojiljkovic M Clinical genetics 2006 PMID: 16879198
Mutational spectrum in German patients with phenylalanine hydroxylase deficiency. Aulehla-Scholz C Human mutation 2003 PMID: 12655553
The molecular basis of phenylketonuria in Lithuania. Kasnauskiene J Human mutation 2003 PMID: 12655550
Phenylketonuria mutations in Germany. Zschocke J Human genetics 1999 PMID: 10394930
Mutations Ivs4nt1, 47delCT, and G148S identified in the phenylalanine hydroxylase gene by RT-PCR of illegitimate transcripts and chemical cleavage of mismatch. Ramus SJ Human mutation 1995 PMID: 8535445
Characterization of phenylalanine hydroxylase alleles in untreated phenylketonuria patients from Victoria, Australia: origin of alleles and haplotypes. Ramus SJ American journal of human genetics 1995 PMID: 7726156
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PAH - - - -
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/88d14684-a7c2-4bfb-9ec0-2e5bc851b285 - - - -

Text-mined citations for rs62642906...

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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 27, 2021