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GeneBe

rs3918290

chr1-97450058-C-Achr1-97450058-C-Gchr1-97450058-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_ModeratePM2_SupportingPP3_Strong

The NM_000110.4(DPYD):c.1905+1G>T variant causes a splice donor change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD Genomes project. In-silico tool predicts a pathogenic outcome for this variant. 2/2 splice prediction tools predicting alterations to normal splicing. 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 splice_donor

Scores

5
1
1
Splicing: ADA: 0.9999
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.57

Links

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PVS1
?
Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.053281352 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
PM2
?
Very rare variant; Number of alleles below threshold, Median coverage is 32.
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DPYDNM_000110.4 linkuse as main transcriptc.1905+1G>T splice_donor_variant ENST00000370192.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DPYDENST00000370192.8 linkuse as main transcriptc.1905+1G>T splice_donor_variant 1 NM_000110.4 P1Q12882-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461520
Hom.:
0
AF XY:
0.00000138
AC XY:
1
AN XY:
727054
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Pathogenic
0.14
Cadd
Pathogenic
33
Dann
Uncertain
0.99
Eigen
Pathogenic
1.1
Eigen_PC
Pathogenic
0.90
FATHMM_MKL
Pathogenic
0.98
D
MutationTaster
Benign
1.0
D
GERP RS
5.3

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.95
SpliceAI score (max)
0.99
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.99
Position offset: 1

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: chr1-97915614;