rs2518608

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4BP6_Very_StrongBP7BS1BS2

The NM_000320.3(QDPR):c.96C>T(p.Ala32Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,610,798 control chromosomes in the GnomAD database, including 156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0080 ( 5 hom., cov: 32)

Exomes 𝑓: 0.012 ( 151 hom. )

Consequence

QDPR
NM_000320.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.78

Publications

2 publications found

Variant links:

Genes affected

QDPR (HGNC:9752): (quinoid dihydropteridine reductase) This gene encodes the enzyme dihydropteridine reductase, which catalyzes the NADH-mediated reduction of quinonoid dihydrobiopterin. This enzyme is an essential component of the pterin-dependent aromatic amino acid hydroxylating systems. Mutations in this gene resulting in QDPR deficiency include aberrant splicing, amino acid substitutions, insertions, or premature terminations. Dihydropteridine reductase deficiency presents as atypical phenylketonuria due to insufficient production of biopterin, a cofactor for phenylalanine hydroxylase. [provided by RefSeq, Jul 2008]

QDPR Gene-Disease associations (from GenCC):

dihydropteridine reductase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

QDPR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.258).

BP6

Variant 4-17511959-G-A is Benign according to our data. Variant chr4-17511959-G-A is described in ClinVar as Benign. ClinVar VariationId is 286391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.78 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00805 (1224/152060) while in subpopulation SAS AF = 0.0133 (64/4818). AF 95% confidence interval is 0.0124. There are 5 homozygotes in GnomAd4. There are 571 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
QDPR	NM_000320.3 link	c.96C>T	p.Ala32Ala	synonymous_variant	Exon 1 of 7	ENST00000281243.10	NP_000311.2	P09417-1A0A140VKA9
QDPR	NM_001306140.2 link	c.96C>T	p.Ala32Ala	synonymous_variant	Exon 1 of 6		NP_001293069.1	P09417-2
QDPR	NR_156494.2 link	n.132C>T		non_coding_transcript_exon_variant	Exon 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
QDPR	ENST00000281243.10 link	c.96C>T	p.Ala32Ala	synonymous_variant	Exon 1 of 7	1	NM_000320.3	ENSP00000281243.5		P09417-1

Frequencies

GnomAD3 genomes

AF:

0.00808

AC:

1228

AN:

151946

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00406

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0137

Gnomad FIN

AF:

0.00463

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.0132

Gnomad OTH

AF:

0.00865

GnomAD2 exomes

AF:

0.0109

AC:

2582

AN:

236828

AF XY:

0.0119

show subpopulations

Gnomad AFR exome

AF:

0.00181

Gnomad AMR exome

AF:

0.00346

Gnomad ASJ exome

AF:

0.0159

Gnomad EAS exome

AF:

0.0000562

Gnomad FIN exome

AF:

0.00601

Gnomad NFE exome

AF:

0.0150

Gnomad OTH exome

AF:

0.0117

GnomAD4 exome

AF:

0.0122

AC:

17730

AN:

1458738

Hom.:

151

Cov.:

AF XY:

0.0125

AC XY:

9054

AN XY:

725738

show subpopulations

African (AFR)

AF:

0.00165

AC:

AN:

33402

American (AMR)

AF:

0.00320

AC:

143

AN:

44650

Ashkenazi Jewish (ASJ)

AF:

0.0150

AC:

391

AN:

26068

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39638

South Asian (SAS)

AF:

0.0184

AC:

1583

AN:

86184

European-Finnish (FIN)

AF:

0.00658

AC:

340

AN:

51706

Middle Eastern (MID)

AF:

0.0248

AC:

143

AN:

5760

European-Non Finnish (NFE)

AF:

0.0130

AC:

14399

AN:

1111132

Other (OTH)

AF:

0.0112

AC:

674

AN:

60198

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

851

1702

2553

3404

4255

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

506

1012

1518

2024

2530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00805

AC:

1224

AN:

152060

Hom.:

Cov.:

AF XY:

0.00768

AC XY:

571

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00181

AC:

AN:

41494

American (AMR)

AF:

0.00405

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0164

AC:

AN:

3466

East Asian (EAS)

AF:

0.000194

AC:

AN:

5162

South Asian (SAS)

AF:

0.0133

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00463

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0131

AC:

893

AN:

67926

Other (OTH)

AF:

0.00856

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

112

167

223

279

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0129

Hom.:

Bravo

AF:

0.00737

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.0148

EpiControl

AF:

0.0153

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Dihydropteridine reductase deficiency

Benign:3

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:2

Feb 29, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

1.8

PromoterAI

-0.21

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over