NM_000320.3(QDPR):c.508G>A (p.Gly170Ser) AND Dihydropteridine reductase deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 30, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001378367.5

Allele description [Variation Report for NM_000320.3(QDPR):c.508G>A (p.Gly170Ser)]

NM_000320.3(QDPR):c.508G>A (p.Gly170Ser)

Gene:

QDPR:quinoid dihydropteridine reductase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4p15.32

Genomic location:

Preferred name:

NM_000320.3(QDPR):c.508G>A (p.Gly170Ser)

HGVS:

NC_000004.12:g.17492269C>T
NG_008763.1:g.24966G>A
NM_000320.3:c.508G>AMANE SELECT
NM_001306140.2:c.415G>A
NP_000311.2:p.Gly170Ser
NP_001293069.1:p.Gly139Ser
NC_000004.11:g.17493892C>T

Protein change:

G139S

Links:

dbSNP: rs769460415

NCBI 1000 Genomes Browser:

rs769460415

Molecular consequence:

NM_000320.3:c.508G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001306140.2:c.415G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Dihydropteridine reductase deficiency (HPABH4C)
Synonyms:: HYPERPHENYLALANINEMIA, TETRAHYDROBIOPTERIN-DEFICIENT, DUE TO DHPR DEFICIENCY; Quinoid dihydropteridine reductase deficiency; Phenylketonuria II; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009862; MedGen: C0268465; Orphanet: 226; Orphanet: 238583; OMIM: 261630

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001575919	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 30, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 8518287, 11694255, 30221392, 32905092, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001575919

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 30, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Identification and in vitro expression of mutations causing dihydropteridine reductase deficiency.

Smooker PM, Howells DW, Cotton RG.

Biochemistry. 1993 Jun 29;32(25):6443-9.

PubMed [citation]

PMID:: 8518287

Tetrahydrobiopterin-deficient hyperphenylalaninemia in the Chinese.

Liu TT, Chiang SH, Wu SJ, Hsiao KJ.

Clin Chim Acta. 2001 Nov;313(1-2):157-69.

PubMed [citation]

PMID:: 11694255

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001575919.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on QDPR function (PMID: 11694255). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1067174). This variant is also known as G523A (Gly170Thr). This missense change has been observed in individual(s) with tetrahydrobiopterin-deficient hyperphenylalaninemia (PMID: 8518287, 11694255, 30221392, 32905092). This variant is present in population databases (rs769460415, gnomAD 0.0009%). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 170 of the QDPR protein (p.Gly170Ser). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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