1-97098521-AAC-A
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000110.4(DPYD):c.2732_2733del(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
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 made for transcript
Verdict is Pathogenic. Variant got 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 id is 2674914.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DPYD | NM_000110.4 | c.2732_2733del | p.Cys911PhefsTer26 | frameshift_variant | 21/23 | ENST00000370192.8 | NP_000101.2 | |
DPYD-AS1 | NR_046590.1 | n.64+2537_64+2538del | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DPYD | ENST00000370192.8 | c.2732_2733del | p.Cys911PhefsTer26 | frameshift_variant | 21/23 | 1 | NM_000110.4 | ENSP00000359211 | P1 | |
DPYD-AS1 | ENST00000422980.1 | n.64+2537_64+2538del | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460848Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 726756
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Dihydropyrimidine dehydrogenase deficiency Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jul 29, 2023 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at