NM_133433.4(NIPBL):c.2207del (p.Pro736fs) AND Cornelia de Lange syndrome 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 17, 2020
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:: RCV001390162.5

Allele description [Variation Report for NM_133433.4(NIPBL):c.2207del (p.Pro736fs)]

NM_133433.4(NIPBL):c.2207del (p.Pro736fs)

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.2207del (p.Pro736fs)

HGVS:

NC_000005.10:g.36985387del
NG_006987.2:g.113505del
NM_015384.5:c.2207del
NM_133433.4:c.2207delMANE SELECT
NP_056199.2:p.Pro736fs
NP_597677.2:p.Pro736fs
NC_000005.9:g.36985488del
NC_000005.9:g.36985489del

Protein change:

P736fs

Links:

dbSNP: rs2149644816

NCBI 1000 Genomes Browser:

rs2149644816

Molecular consequence:

NM_015384.5:c.2207del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_133433.4:c.2207del - frameshift variant - [Sequence Ontology: SO:0001589]

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

Recent activity

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interferon alpha-inducible protein 27, mitochondrial isoform 1 [Homo sapiens]
interferon alpha-inducible protein 27, mitochondrial isoform 1 [Homo sapiens]
gi|572879007|ref|NP_001275885.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001591799	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 17, 2020)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 15318302, 19763162, 23505322, 29995837, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001591799

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 17, 2020)

germline

clinical testing

PubMed (5)
[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

NIPBL mutational analysis in 120 individuals with Cornelia de Lange syndrome and evaluation of genotype-phenotype correlations.

Gillis LA, McCallum J, Kaur M, DeScipio C, Yaeger D, Mariani A, Kline AD, Li HH, Devoto M, Jackson LG, Krantz ID.

Am J Hum Genet. 2004 Oct;75(4):610-23. Epub 2004 Aug 18.

PubMed [citation]

PMID:: 15318302
PMCID:: PMC1182048

Multiple organ system defects and transcriptional dysregulation in the Nipbl(+/-) mouse, a model of Cornelia de Lange Syndrome.

Kawauchi S, Calof AL, Santos R, Lopez-Burks ME, Young CM, Hoang MP, Chua A, Lao T, Lechner MS, Daniel JA, Nussenzweig A, Kitzes L, Yokomori K, Hallgrimsson B, Lander AD.

PLoS Genet. 2009 Sep;5(9):e1000650. doi: 10.1371/journal.pgen.1000650. Epub 2009 Sep 18.

PubMed [citation]

PMID:: 19763162
PMCID:: PMC2730539

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001591799.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in NIPBL are known to be pathogenic (PMID: 15318302, 19763162, 23505322, 29995837). This variant has not been reported in the literature in individuals with NIPBL-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Pro736Glnfs*58) in the NIPBL gene. It is expected to result in an absent or disrupted protein product.

#	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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