NM_203486.3(DLL3):c.1339_1340insT (p.His447fs) AND Spondylocostal dysostosis 1, autosomal recessive

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 1, 2022
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:: RCV002283621.1

Allele description [Variation Report for NM_203486.3(DLL3):c.1339_1340insT (p.His447fs)]

NM_203486.3(DLL3):c.1339_1340insT (p.His447fs)

Gene:

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

Variant type:

Insertion

Cytogenetic location:

19q13.2

Genomic location:

Preferred name:

NM_203486.3(DLL3):c.1339_1340insT (p.His447fs)

HGVS:

NC_000019.10:g.39507284_39507285insT
NG_008256.1:g.13368_13369insT
NM_016941.4:c.1339_1340insT
NM_203486.3:c.1339_1340insTMANE SELECT
NP_058637.1:p.His447fs
NP_982353.1:p.His447fs
NC_000019.9:g.39997924_39997925insT

Protein change:

H447fs

Molecular consequence:

NM_016941.4:c.1339_1340insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_203486.3:c.1339_1340insT - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

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
SCV002572556	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 1, 2022)	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

SCV002572556

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Sep 1, 2022)

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	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

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 3billion, SCV002572556.1

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

Description

The variant is not observed in the gnomAD v2.1.1 dataset. It is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. Therefore, this homozygous variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.

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

Last Updated: Sep 24, 2022

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