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GeneBe

rs1801160

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_000110.4(DPYD):c.2194G>C(p.Val732Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD Genomes project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V732I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

DPYD
NM_000110.4 missense

Scores

4
11
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.50
Variant links:
Genes affected
DPYD (HGNC:3012): (dihydropyrimidine dehydrogenase) The protein encoded by this gene is a pyrimidine catabolic enzyme and the initial and rate-limiting factor in the pathway of uracil and thymidine catabolism. Mutations in this gene result in dihydropyrimidine dehydrogenase deficiency, an error in pyrimidine metabolism associated with thymine-uraciluria and an increased risk of toxicity in cancer patients receiving 5-fluorouracil chemotherapy. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]
DPYD-AS1 (HGNC:40195): (DPYD antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.809

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DPYDNM_000110.4 linkuse as main transcriptc.2194G>C p.Val732Leu missense_variant 18/23 ENST00000370192.8
DPYD-AS1NR_046590.1 linkuse as main transcriptn.129-825C>G intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DPYDENST00000370192.8 linkuse as main transcriptc.2194G>C p.Val732Leu missense_variant 18/231 NM_000110.4 P1Q12882-1
DPYD-AS1ENST00000422980.1 linkuse as main transcriptn.129-825C>G intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.58
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Uncertain
0.060
Cadd
Uncertain
23
Dann
Uncertain
1.0
DEOGEN2
Uncertain
0.47
T
Eigen
Uncertain
0.67
Eigen_PC
Uncertain
0.66
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
D
M_CAP
Benign
0.027
D
MetaRNN
Pathogenic
0.81
D
MetaSVM
Uncertain
-0.12
T
MutationAssessor
Benign
1.6
L
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.61
T
PROVEAN
Uncertain
-2.9
D
REVEL
Uncertain
0.59
Sift
Uncertain
0.020
D
Sift4G
Benign
0.10
T
Polyphen
0.99
D
Vest4
0.77
MutPred
0.50
Loss of sheet (P = 0.1398);
MVP
0.91
MPC
0.15
ClinPred
0.97
D
GERP RS
5.5
Varity_R
0.58
gMVP
0.87

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-97770920; API