chr19-39500597-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_203486.3(DLL3):c.352-18C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 1,605,918 control chromosomes in the GnomAD database, including 84,600 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6497 hom., cov: 30)

Exomes 𝑓: 0.32 ( 78103 hom. )

Consequence

DLL3
NM_203486.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0640

Publications

13 publications found

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 Gene-Disease associations (from GenCC):

spondylocostal dysostosis 1, autosomal recessive
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
autosomal recessive spondylocostal dysostosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

DLL3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 19-39500597-C-G is Benign according to our data. Variant chr19-39500597-C-G is described in ClinVar as Benign. ClinVar VariationId is 260778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLL3	NM_203486.3 link	c.352-18C>G		intron_variant	Intron 2 of 8	ENST00000356433.10	NP_982353.1	Q9NYJ7-2
DLL3	NM_016941.4 link	c.352-18C>G		intron_variant	Intron 2 of 7		NP_058637.1	Q9NYJ7-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DLL3	ENST00000356433.10 link	c.352-18C>G	intron_variant	Intron 2 of 8	2	NM_203486.3	ENSP00000348810.4	Q9NYJ7-2
DLL3	ENST00000205143.4 link	c.352-18C>G	intron_variant	Intron 2 of 7	1		ENSP00000205143.3	Q9NYJ7-1
DLL3	ENST00000600437.1 link	n.432-18C>G	intron_variant	Intron 2 of 5	1
DLL3	ENST00000596614.5 link	c.352-18C>G	intron_variant	Intron 2 of 3	2		ENSP00000471688.1	M0R177

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42855

AN:

151854

Hom.:

6498

Cov.:

show subpopulations

Gnomad AFR

AF:

0.174

Gnomad AMI

AF:

0.309

Gnomad AMR

AF:

0.288

Gnomad ASJ

AF:

0.293

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.343

Gnomad FIN

AF:

0.385

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.336

Gnomad OTH

AF:

0.297

GnomAD2 exomes

AF:

0.307

AC:

77079

AN:

251454

AF XY:

0.313

show subpopulations

Gnomad AFR exome

AF:

0.171

Gnomad AMR exome

AF:

0.308

Gnomad ASJ exome

AF:

0.294

Gnomad EAS exome

AF:

0.116

Gnomad FIN exome

AF:

0.386

Gnomad NFE exome

AF:

0.334

Gnomad OTH exome

AF:

0.332

GnomAD4 exome

AF:

0.323

AC:

469227

AN:

1453946

Hom.:

78103

Cov.:

AF XY:

0.325

AC XY:

234910

AN XY:

723654

show subpopulations

African (AFR)

AF:

0.168

AC:

5587

AN:

33352

American (AMR)

AF:

0.307

AC:

13726

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.292

AC:

7609

AN:

26062

East Asian (EAS)

AF:

0.113

AC:

4478

AN:

39636

South Asian (SAS)

AF:

0.333

AC:

28660

AN:

86112

European-Finnish (FIN)

AF:

0.390

AC:

20769

AN:

53266

Middle Eastern (MID)

AF:

0.383

AC:

2200

AN:

5750

European-Non Finnish (NFE)

AF:

0.332

AC:

367317

AN:

1104998

Other (OTH)

AF:

0.314

AC:

18881

AN:

60086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

Heterozygous variant carriers

15391

30782

46173

61564

76955

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11652

23304

34956

46608

58260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.282

AC:

42855

AN:

151972

Hom.:

6497

Cov.:

AF XY:

0.286

AC XY:

21250

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.174

AC:

7211

AN:

41476

American (AMR)

AF:

0.288

AC:

4395

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.293

AC:

1018

AN:

3472

East Asian (EAS)

AF:

0.125

AC:

645

AN:

5174

South Asian (SAS)

AF:

0.345

AC:

1659

AN:

4814

European-Finnish (FIN)

AF:

0.385

AC:

4056

AN:

10548

Middle Eastern (MID)

AF:

0.412

AC:

121

AN:

294

European-Non Finnish (NFE)

AF:

0.336

AC:

22853

AN:

67942

Other (OTH)

AF:

0.293

AC:

616

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1560

3120

4681

6241

7801

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

446

892

1338

1784

2230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.252

Hom.:

962

Bravo

AF:

0.267

Asia WGS

AF:

0.227

AC:

790

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 21, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Spondylocostal dysostosis 1, autosomal recessive

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

6.4

(source)

DANN

Benign

0.78

PhyloP100

0.064

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over