NM_203486.3(DLL3):c.945_946del (p.Ala317fs) AND Spondylocostal dysostosis 1, autosomal recessive

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jun 28, 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:: RCV000007231.4

Allele description [Variation Report for NM_203486.3(DLL3):c.945_946del (p.Ala317fs)]

NM_203486.3(DLL3):c.945_946del (p.Ala317fs)

Gene:

DLL3:delta like canonical Notch ligand 3 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

19q13.2

Genomic location:

Preferred name:

NM_203486.3(DLL3):c.945_946del (p.Ala317fs)

HGVS:

NC_000019.10:g.39505303_39505304del
NG_008256.1:g.11387_11388del
NM_016941.4:c.945_946del
NM_203486.3:c.945_946delMANE SELECT
NP_058637.1:p.Ala317fs
NP_982353.1:p.Ala317fs
NC_000019.9:g.39995943_39995944del
NM_016941.3:c.945_946del

Note:

NCBI staff reviewed the sequence information reported in PubMed 10742114 Fig. 3b to determine the location of this allele on the current reference sequence.

Protein change:

A317fs

Links:

OMIM: 602768.0002; dbSNP: rs786200900

NCBI 1000 Genomes Browser:

rs786200900

Molecular consequence:

NM_016941.4:c.945_946del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_203486.3:c.945_946del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Spondylocostal dysostosis 1, autosomal recessive (SCDO1)
Identifiers:: MONDO: MONDO:0020692; MedGen: CN032975; Orphanet: 2311; OMIM: 277300

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000027427	OMIM	no assertion criteria provided	Pathogenic (Apr 1, 2000)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV003935296	Department of Human Genetics, Hannover Medical School	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 28, 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

SCV000027427

OMIM

no assertion criteria provided

Pathogenic
(Apr 1, 2000)

germline

literature only

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

SCV003935296

Department of Human Genetics, Hannover Medical School

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jun 28, 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

Mutations in the human delta homologue, DLL3, cause axial skeletal defects in spondylocostal dysostosis.

Bulman MP, Kusumi K, Frayling TM, McKeown C, Garrett C, Lander ES, Krumlauf R, Hattersley AT, Ellard S, Turnpenny PD.

Nat Genet. 2000 Apr;24(4):438-41.

PubMed [citation]

PMID:: 10742114

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, SCV000027427.2

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

Description

In a family from Rawalpindi, Pakistan segregating autosomal recessive spondylocostal dysostosis (SCDO1; 277300), Bulman et al. (2000) identified a 2-bp deletion (AT) resulting in a frameshift in exon 7 of the DLL3 gene. As expected, this mutation was found in homozygous state in all affected individuals.

#	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 Department of Human Genetics, Hannover Medical School, SCV003935296.1

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

#	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: Sep 29, 2024

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