rs771648776

Positions:

• chr1-97515812-T-A
• chr1-97515812-T-C
• chr1-97515812-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000110.4(DPYD):​c.1654A>T​(p.Thr552Ser) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DPYD NM_000110.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.27

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30493438).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPYD	NM_000110.4	c.1654A>T	p.Thr552Ser	missense_variant	13/23	ENST00000370192.8	NP_000101.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPYD	ENST00000370192.8	c.1654A>T	p.Thr552Ser	missense_variant	13/23	1	NM_000110.4	ENSP00000359211	P1

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	0.32
BayesDel_addAF	Benign	0.0053	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.30	T
MetaSVM	Uncertain	0.021	D
MutationAssessor	Uncertain	2.6	M
MutationTaster	Benign	0.94	D
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.71	N
REVEL	Uncertain	0.46
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.096	B
Vest4		0.15
MutPred		0.70		Gain of disorder (P = 0.0436);
MVP		0.87
MPC		0.056
ClinPred		0.88	D
GERP RS		4.0
Varity_R		0.25
gMVP		0.76

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-97981368;