NM_005618.4(DLL1):c.1525C>T (p.Arg509Ter) AND Neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 23, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000984542.3

Allele description [Variation Report for NM_005618.4(DLL1):c.1525C>T (p.Arg509Ter)]

NM_005618.4(DLL1):c.1525C>T (p.Arg509Ter)

Gene:

DLL1:delta like canonical Notch ligand 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6q27

Genomic location:

Preferred name:

NM_005618.4(DLL1):c.1525C>T (p.Arg509Ter)

HGVS:

NC_000006.12:g.170283754G>A
NG_027940.1:g.11856C>T
NM_005618.4:c.1525C>TMANE SELECT
NP_005609.3:p.Arg509Ter
NC_000006.11:g.170592842G>A
NM_005618.3:c.1525C>T

Protein change:

R509*; ARG509TER

Links:

OMIM: 606582.0003; dbSNP: rs1583152162

NCBI 1000 Genomes Browser:

rs1583152162

Molecular consequence:

NM_005618.4:c.1525C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures
Identifiers:: MONDO: MONDO:0032877; MedGen: C5231470; OMIM: 618709

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001132601	OMIM	no assertion criteria provided	Pathogenic (Dec 20, 2019)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV003932220	Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 23, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001132601

OMIM

no assertion criteria provided

Pathogenic
(Dec 20, 2019)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV003932220

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 23, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Haploinsufficiency of the Notch Ligand DLL1 Causes Variable Neurodevelopmental Disorders.

Fischer-Zirnsak B, Segebrecht L, Schubach M, Charles P, Alderman E, Brown K, Cadieux-Dion M, Cartwright T, Chen Y, Costin C, Fehr S, Fitzgerald KM, Fleming E, Foss K, Ha T, Hildebrand G, Horn D, Liu S, Marco EJ, McDonald M, McWalter K, Race S, et al.

Am J Hum Genet. 2019 Sep 5;105(3):631-639. doi: 10.1016/j.ajhg.2019.07.002. Epub 2019 Jul 25.

PubMed [citation]

PMID:: 31353024
PMCID:: PMC6731356

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From OMIM, SCV001132601.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In an 8-year-old boy (individual 6) with neurodevelopmental disorder with nonspecific brain abnormalities and seizures (NEDBAS; 618709), Fischer-Zirnsak et al. (2019) identified a heterozygous c.1525C-T transition (c.1525C-T, NM_005618.3) in exon 9 of the DLL1 gene, resulting in an arg509-to-ter (R509X) substitution. The mutation, which was found by exome sequencing, was inherited from the affected father. The mutation was not present in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed, but the variant was predicted to result in haploinsufficiency.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center, SCV003932220.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

PVS1, PS4_Moderate, PM2

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 15, 2024

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