Genetic Variant DPYD:c.2622+230G>A (chr1-97192839-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000110.4(DPYD):c.2622+230G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 152,012 control chromosomes in the GnomAD database, including 32,407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.65 ( 32407 hom., cov: 31)

Consequence

DPYD
NM_000110.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.800

Publications

5 publications found

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:

DPYD-AS1 (HGNC:40195): (DPYD antisense RNA 1)

DPYD-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 1-97192839-C-T is Benign according to our data. Variant chr1-97192839-C-T is described in ClinVar as Benign. ClinVar VariationId is 1267185.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

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.2622+230G>A		intron	N/A	NP_000101.2	Q12882-1
	DPYD-AS1	NR_046590.1		n.65-72575C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DPYD	ENST00000370192.8	TSL:1 MANE Select	c.2622+230G>A	intron	N/A	ENSP00000359211.3	Q12882-1
DPYD	ENST00000876340.1		c.2790+230G>A	intron	N/A	ENSP00000546399.1
DPYD	ENST00000969915.1		c.2622+230G>A	intron	N/A	ENSP00000639974.1

Frequencies

GnomAD3 genomes

AF:

0.649

AC:

98521

AN:

151894

Hom.:

32375

Cov.:

show subpopulations

Gnomad AFR

AF:

0.656

Gnomad AMI

AF:

0.512

Gnomad AMR

AF:

0.654

Gnomad ASJ

AF:

0.561

Gnomad EAS

AF:

0.991

Gnomad SAS

AF:

0.815

Gnomad FIN

AF:

0.624

Gnomad MID

AF:

0.649

Gnomad NFE

AF:

0.615

Gnomad OTH

AF:

0.644

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.649

AC:

98606

AN:

152012

Hom.:

32407

Cov.:

AF XY:

0.654

AC XY:

48594

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.656

AC:

27218

AN:

41462

American (AMR)

AF:

0.655

AC:

9997

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.561

AC:

1947

AN:

3468

East Asian (EAS)

AF:

0.991

AC:

5109

AN:

5154

South Asian (SAS)

AF:

0.816

AC:

3932

AN:

4820

European-Finnish (FIN)

AF:

0.624

AC:

6586

AN:

10552

Middle Eastern (MID)

AF:

0.650

AC:

191

AN:

294

European-Non Finnish (NFE)

AF:

0.615

AC:

41800

AN:

67972

Other (OTH)

AF:

0.645

AC:

1359

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1741

3482

5224

6965

8706

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

806

1612

2418

3224

4030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.636

Hom.:

13950

Bravo

AF:

0.652

Asia WGS

AF:

0.869

AC:

3019

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

9.1

(source)

DANN

Benign

0.57

PhyloP100

0.80

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over