Variant 19-39499187-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_203486.3(DLL3):c.70-5C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000126 in 1,584,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

DLL3
NM_203486.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.002603

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.786

Variant links:

Genes affected

DLL3 (HGNC:2909): (delta like canonical Notch ligand 3) This gene encodes a member of the delta protein ligand family. This family functions as Notch ligands that are characterized by a DSL domain, EGF repeats, and a transmembrane domain. Mutations in this gene cause autosomal recessive spondylocostal dysostosis 1. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

DLL3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 19-39499187-C-G is Benign according to our data. Variant chr19-39499187-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2989643.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLL3	NM_203486.3 linkuse as main transcript	c.70-5C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000356433.10	NP_982353.1
DLL3	NM_016941.4 linkuse as main transcript	c.70-5C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_058637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLL3	ENST00000356433.10 linkuse as main transcript	c.70-5C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2	NM_203486.3	ENSP00000348810	P1	Q9NYJ7-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.98e-7

AC:

AN:

1432334

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

711470

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:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 03, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

9.0

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0026

dbscSNV1_RF

Benign

0.040

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.22

Position offset: 5

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over