rs2597773

Variant names:

• chr4-17496544-T-G
• rs2597773
• NM_000320.3:c.437-4204A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000320.3(QDPR):​c.437-4204A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 150,476 control chromosomes in the GnomAD database, including 6,612 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6612 hom., cov: 29)
• Consequence: QDPR NM_000320.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.852
• Publications: 1 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000320.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	QDPR	NM_000320.3	MANE Select	c.437-4204A>C		intron	N/A	NP_000311.2
	QDPR	NM_001306140.2		c.344-4204A>C		intron	N/A	NP_001293069.1
	QDPR	NR_156494.2		n.472+5175A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	QDPR	ENST00000281243.10	TSL:1 MANE Select	c.437-4204A>C		intron	N/A	ENSP00000281243.5
	QDPR	ENST00000910937.1		c.512-4204A>C		intron	N/A	ENSP00000580996.1
	QDPR	ENST00000910936.1		c.485-4204A>C		intron	N/A	ENSP00000580995.1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 42652 AN: 150376 Hom.: 6606 Cov.: 29

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.0184

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.299

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.284 AC: 42679 AN: 150476 Hom.: 6612 Cov.: 29 AF XY: 0.281 AC XY: 20597 AN XY: 73374

African (AFR) AF: 0.230 AC: 9437 AN: 40996

American (AMR) AF: 0.238 AC: 3605 AN: 15120

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1082 AN: 3460

East Asian (EAS) AF: 0.0184 AC: 95 AN: 5150

South Asian (SAS) AF: 0.383 AC: 1814 AN: 4732

European-Finnish (FIN) AF: 0.304 AC: 3062 AN: 10084

Middle Eastern (MID) AF: 0.379 AC: 110 AN: 290

European-Non Finnish (NFE) AF: 0.334 AC: 22621 AN: 67650

Other (OTH) AF: 0.296 AC: 620 AN: 2092

Alfa AF: 0.307 Hom.: 3115

Bravo AF: 0.270

Asia WGS AF: 0.182 AC: 634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	5.9
DANN	Benign	0.86
PhyloP100		0.85
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2597773; hg19: chr4-17498167;