rs1555393082

Positions:

• chr15-40935122-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000249749.7(DLL4):​c.1240+5G>C variant causes a splice donor 5th base, intron 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. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DLL4 ENST00000249749.7 splice_donor_5th_base, intron
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.84

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLL4	NM_019074.4	c.1240+5G>C		splice_donor_5th_base_variant, intron_variant		ENST00000249749.7	NP_061947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLL4	ENST00000249749.7	c.1240+5G>C		splice_donor_5th_base_variant, intron_variant		1	NM_019074.4	ENSP00000249749	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Adams-Oliver syndrome 6 Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Centre of Medical Genetics, University of Antwerp

Dec 01, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Pathogenic	32
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.91
SpliceAI score (max)		0.71		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.71		Position offset: -31
DS_DL_spliceai		0.27		Position offset: -5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1555393082; hg19: chr15-41227320;