rs1801265

Variant names:

• chr1-97883329-A-C
• rs1801265
• NM_000110.4:c.85T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-97883329-A-C
• chr1-97883329-A-G
• chr1-97883329-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000110.4(DPYD):​c.85T>G​(p.Cys29Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign 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. C29R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DPYD NM_000110.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65
• 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]

DPYD Gene-Disease associations (from GenCC):

• dihydropyrimidine dehydrogenase deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21800369).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPYD	NM_000110.4	c.85T>G	p.Cys29Gly	missense_variant	Exon 2 of 23	ENST00000370192.8	NP_000101.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYD	ENST00000370192.8	c.85T>G	p.Cys29Gly	missense_variant	Exon 2 of 23	1	NM_000110.4	ENSP00000359211.3
DPYD	ENST00000306031.5	c.85T>G	p.Cys29Gly	missense_variant	Exon 2 of 6	1		ENSP00000307107.5
DPYD	ENST00000460019.1	n.160T>G		non_coding_transcript_exon_variant	Exon 2 of 3	2
DPYD	ENST00000646851.1	n.734T>G		non_coding_transcript_exon_variant	Exon 6 of 6

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	Benign	0.10
BayesDel_noAF	Uncertain	0.020
CADD	Benign	18
DEOGEN2	Benign	0.095	T;.
LIST_S2	Benign	0.26	T;T
MetaRNN	Benign	0.22	T;T
PhyloP100		1.6
Sift4G	Benign	0.33	T;T
Vest4		0.20
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1801265; hg19: chr1-98348885;