NM_000110.4:c.2732_2733delGT
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000110.4(DPYD):c.2732_2733delGT(p.Cys911PhefsTer26) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,848 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
DPYD
NM_000110.4 frameshift
NM_000110.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.208
Publications
0 publications found
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]
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-97098521-AAC-A is Pathogenic according to our data. Variant chr1-97098521-AAC-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 2674914.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000110.4. 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 |
|---|---|---|---|---|---|---|---|---|---|
| DPYD | NM_000110.4 | MANE Select | c.2732_2733delGT | p.Cys911PhefsTer26 | frameshift | Exon 21 of 23 | NP_000101.2 | Q12882-1 | |
| DPYD-AS1 | NR_046590.1 | n.64+2537_64+2538delCA | intron | N/A |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DPYD | ENST00000370192.8 | TSL:1 MANE Select | c.2732_2733delGT | p.Cys911PhefsTer26 | frameshift | Exon 21 of 23 | ENSP00000359211.3 | Q12882-1 | |
| DPYD | ENST00000876340.1 | c.2900_2901delGT | p.Cys967PhefsTer26 | frameshift | Exon 22 of 24 | ENSP00000546399.1 | |||
| DPYD | ENST00000969915.1 | c.2837_2838delGT | p.Cys946PhefsTer26 | frameshift | Exon 22 of 24 | ENSP00000639974.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460848Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 726756 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1460848
Hom.:
AF XY:
AC XY:
1
AN XY:
726756
show subpopulations
African (AFR)
AF:
AC:
1
AN:
33416
American (AMR)
AF:
AC:
0
AN:
44690
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26098
East Asian (EAS)
AF:
AC:
0
AN:
39590
South Asian (SAS)
AF:
AC:
0
AN:
86240
European-Finnish (FIN)
AF:
AC:
0
AN:
53326
Middle Eastern (MID)
AF:
AC:
0
AN:
5752
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111406
Other (OTH)
AF:
AC:
0
AN:
60330
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
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0
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2
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions
View on ClinVar Significance:Likely pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Dihydropyrimidine dehydrogenase deficiency (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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