rs796065344

Variant names:

• chr15-40936647-C-G
• NM_019074.4:c.1660C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-40936647-C-G
• chr15-40936647-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_019074.4(DLL4):​c.1660C>G​(p.Gln554Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DLL4 NM_019074.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.17

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the DLL4 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 15 curated pathogenic missense variants (we use a threshold of 10). The gene has 12 curated benign missense variants. Gene score misZ: 2.7062 (below the threshold of 3.09). Trascript score misZ: 3.8915 (above the threshold of 3.09). GenCC associations: The gene is linked to Adams-Oliver syndrome, aplasia cutis congenita, Adams-Oliver syndrome 6.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLL4	NM_019074.4	c.1660C>G	p.Gln554Glu	missense_variant	Exon 9 of 11	ENST00000249749.7	NP_061947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLL4	ENST00000249749.7	c.1660C>G	p.Gln554Glu	missense_variant	Exon 9 of 11	1	NM_019074.4	ENSP00000249749.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	T;T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.72	.;T
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Benign	1.1	L;L
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.97	.;N
REVEL	Uncertain	0.40
Sift	Benign	0.065	.;T
Sift4G	Benign	0.32	.;T
Polyphen		0.69	P;P
Vest4		0.47
MutPred		0.44		Loss of MoRF binding (P = 0.0398);Loss of MoRF binding (P = 0.0398);
MVP		0.66
MPC		0.70
ClinPred		0.94	D
GERP RS		5.9
Varity_R		0.27
gMVP		0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-41228845;