Genetic Variant DPYD:c.2908-69A>G (chr1-97079215-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000110.4(DPYD):c.2908-69A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.829 in 1,566,256 control chromosomes in the GnomAD database, including 539,716 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 49303 hom., cov: 31)

Exomes 𝑓: 0.83 ( 490413 hom. )

Consequence

DPYD
NM_000110.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.557

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 1-97079215-T-C is Benign according to our data. Variant chr1-97079215-T-C is described in ClinVar as [Benign]. Clinvar id is 1222833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPYD	NM_000110.4 link	c.2908-69A>G		intron_variant	Intron 22 of 22	ENST00000370192.8	NP_000101.2	Q12882-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYD	ENST00000370192.8 link	c.2908-69A>G		intron_variant	Intron 22 of 22	1	NM_000110.4	ENSP00000359211.3		Q12882-1

Frequencies

GnomAD3 genomes

AF:

0.802

AC:

121924

AN:

151960

Hom.:

49271

Cov.:

show subpopulations

Gnomad AFR

AF:

0.710

Gnomad AMI

AF:

0.884

Gnomad AMR

AF:

0.868

Gnomad ASJ

AF:

0.847

Gnomad EAS

AF:

0.988

Gnomad SAS

AF:

0.892

Gnomad FIN

AF:

0.839

Gnomad MID

AF:

0.820

Gnomad NFE

AF:

0.813

Gnomad OTH

AF:

0.816

GnomAD4 exome

AF:

0.831

AC:

1175814

AN:

1414178

Hom.:

490413

AF XY:

0.833

AC XY:

588326

AN XY:

706420

show subpopulations

Gnomad4 AFR exome

AF:

0.705

Gnomad4 AMR exome

AF:

0.889

Gnomad4 ASJ exome

AF:

0.840

Gnomad4 EAS exome

AF:

0.994

Gnomad4 SAS exome

AF:

0.902

Gnomad4 FIN exome

AF:

0.838

Gnomad4 NFE exome

AF:

0.821

Gnomad4 OTH exome

AF:

0.829

GnomAD4 genome

AF:

0.802

AC:

122014

AN:

152078

Hom.:

49303

Cov.:

AF XY:

0.808

AC XY:

60087

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.711

Gnomad4 AMR

AF:

0.868

Gnomad4 ASJ

AF:

0.847

Gnomad4 EAS

AF:

0.988

Gnomad4 SAS

AF:

0.892

Gnomad4 FIN

AF:

0.839

Gnomad4 NFE

AF:

0.813

Gnomad4 OTH

AF:

0.817

Alfa

AF:

0.816

Hom.:

66383

Bravo

AF:

0.802

Asia WGS

AF:

0.913

AC:

3175

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

6.1

DANN

Benign

0.24

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over