NM_133433.4(NIPBL):c.64+2_64+134del AND Cornelia de Lange syndrome 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 14, 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:: RCV001043668.2

Allele description [Variation Report for NM_133433.4(NIPBL):c.64+2_64+134del]

NM_133433.4(NIPBL):c.64+2_64+134del

Gene:

NIPBL:NIPBL cohesin loading factor [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

5p13.2

Genomic location:

Preferred name:

NM_133433.4(NIPBL):c.64+2_64+134del

HGVS:

NC_000005.10:g.36953762_36953894del
NG_006987.2:g.81880_82012del
NM_015384.5:c.64+2_64+134del
NM_133433.4:c.64+2_64+134delMANE SELECT
NC_000005.9:g.36953864_36953996del
NG_006987.1:g.81880_82012del
NM_133433.3:c.64+2_64+134del

Links:

dbSNP: rs1740652803

NCBI 1000 Genomes Browser:

rs1740652803

Molecular consequence:

NM_015384.5:c.64+2_64+134del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_133433.4:c.64+2_64+134del - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Cornelia de Lange syndrome 1 (CDLS1)
Synonyms:: Typus degenerativus amstelodamensis; Brachmann de Lange syndrome
Identifiers:: MONDO: MONDO:0007387; MedGen: C4551851; Orphanet: 199; OMIM: 122470

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001207426	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 14, 2019)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 22581668, 15591270, 26701315, 15318302, 19763162, 29995837, 23505322, 25574841, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001207426

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 14, 2019)

germline

clinical testing

PubMed (9)
[See all records that cite these PMIDs]

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

Citations

PubMed

Germline mosaicism in Cornelia de Lange syndrome.

Slavin TP, Lazebnik N, Clark DM, Vengoechea J, Cohen L, Kaur M, Konczal L, Crowe CA, Corteville JE, Nowaczyk MJ, Byrne JL, Jackson LG, Krantz ID.

Am J Med Genet A. 2012 Jun;158A(6):1481-5. doi: 10.1002/ajmg.a.35381. Epub 2012 May 11.

PubMed [citation]

PMID:: 22581668
PMCID:: PMC3356507

NIPBL mutations and genetic heterogeneity in Cornelia de Lange syndrome.

Borck G, Redon R, Sanlaville D, Rio M, Prieur M, Lyonnet S, Vekemans M, Carter NP, Munnich A, Colleaux L, Cormier-Daire V.

J Med Genet. 2004 Dec;41(12):e128. No abstract available.

PubMed [citation]

PMID:: 15591270
PMCID:: PMC1735640

See all PubMed Citations (9)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001207426.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

This sequence change affects a donor splice site in intron 2 of the NIPBL gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in several individuals affected with Cornelia de Lange syndrome (PMID: 15591270, 25574841, 22581668, 26701315). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in NIPBL are known to be pathogenic (PMID: 15318302, 19763162, 23505322, 29995837). For these reasons, this variant has been classified as Pathogenic.

#	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: Sep 29, 2024

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