15-40929980-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2
The NM_019074.4(DLL4):c.200C>T(p.Ala67Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000341 in 1,613,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000034 ( 0 hom. )
Consequence
DLL4
NM_019074.4 missense
NM_019074.4 missense
Scores
5
9
Clinical Significance
Conservation
PhyloP100: 3.64
Genes affected
DLL4 (HGNC:2910): (delta like canonical Notch ligand 4) This gene is a homolog of the Drosophila delta gene. The delta gene family encodes Notch ligands that are characterized by a DSL domain, EGF repeats, and a transmembrane domain. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, DLL4
BP4
?
Computational evidence support a benign effect (MetaRNN=0.34577143).
BS2
?
High AC in GnomAd at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DLL4 | NM_019074.4 | c.200C>T | p.Ala67Val | missense_variant | 2/11 | ENST00000249749.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DLL4 | ENST00000249749.7 | c.200C>T | p.Ala67Val | missense_variant | 2/11 | 1 | NM_019074.4 | P1 | |
DLL4 | ENST00000557876.1 | n.529C>T | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152228Hom.: 0 Cov.: 33
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000446 AC: 11AN: 246450Hom.: 0 AF XY: 0.0000670 AC XY: 9AN XY: 134384
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GnomAD4 exome AF: 0.0000342 AC: 50AN: 1460800Hom.: 0 Cov.: 32 AF XY: 0.0000509 AC XY: 37AN XY: 726672
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GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152346Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74494
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 31, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Uncertain
D;D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Polyphen
B;B
Vest4
0.14
MutPred
Gain of methylation at K63 (P = 0.1286);Gain of methylation at K63 (P = 0.1286);
MVP
0.58
MPC
1.1
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at