NM_203486.3(DLL3):c.1398C>A (p.Phe466Leu) AND Spondylocostal dysostosis 1, autosomal recessive

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 24, 2019
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:: RCV001001363.8

Allele description [Variation Report for NM_203486.3(DLL3):c.1398C>A (p.Phe466Leu)]

NM_203486.3(DLL3):c.1398C>A (p.Phe466Leu)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

19q13.2

Genomic location:

Preferred name:

NM_203486.3(DLL3):c.1398C>A (p.Phe466Leu)

HGVS:

NC_000019.10:g.39507343C>A
NG_008256.1:g.13427C>A
NM_016941.4:c.1398C>A
NM_203486.3:c.1398C>AMANE SELECT
NP_058637.1:p.Phe466Leu
NP_982353.1:p.Phe466Leu
NC_000019.9:g.39997983C>A

Protein change:

F466L

Links:

dbSNP: rs777442783

NCBI 1000 Genomes Browser:

rs777442783

Molecular consequence:

NM_016941.4:c.1398C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_203486.3:c.1398C>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001158561	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Uncertain significance (Jun 24, 2019)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001158561

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)

Uncertain significance
(Jun 24, 2019)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001158561.1

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

Description

The DLL3 c.1398C>A; p.Phe466Leu variant (rs777442783), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is only observed on two alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. The phenylalanine at codon 466 is moderately conserved, and computational analyses (SIFT: damaging, PolyPhen-2: benign) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the p.Phe466Leu variant is uncertain at this time.

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

Last Updated: Mar 4, 2023

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