NM_002485.5(NBN):c.1142del (p.Pro381fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 15, 2021
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:: RCV000130355.11

Allele description [Variation Report for NM_002485.5(NBN):c.1142del (p.Pro381fs)]

NM_002485.5(NBN):c.1142del (p.Pro381fs)

Gene:

NBN:nibrin [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

8q21.3

Genomic location:

Preferred name:

NM_002485.5(NBN):c.1142del (p.Pro381fs)

HGVS:

NC_000008.11:g.89955539del
NG_008860.1:g.34134del
NM_001024688.3:c.896del
NM_002485.5:c.1142delMANE SELECT
NP_001019859.1:p.Pro299fs
NP_002476.2:p.Pro381fs
LRG_158:g.34134del
NC_000008.10:g.90967766del
NC_000008.10:g.90967767del
NM_002485.4:c.1142delC
NM_002485.5:c.1142del
NP_002476.2:p.Pro381GlnfsTer22
p.P381QFS*23

Protein change:

P299fs

Links:

OMIM: 602667.0005; dbSNP: rs587781969

NCBI 1000 Genomes Browser:

rs587781969

Molecular consequence:

NM_001024688.3:c.896del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_002485.5:c.1142del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000185206	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Sep 15, 2021)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 18593981, 24549055, 26270727, 26689913, 30322717 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000185206

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Sep 15, 2021)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

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

Citations

PubMed

Mutations in the Nijmegen breakage syndrome gene in medulloblastomas.

Huang J, Grotzer MA, Watanabe T, Hewer E, Pietsch T, Rutkowski S, Ohgaki H.

Clin Cancer Res. 2008 Jul 1;14(13):4053-8. doi: 10.1158/1078-0432.CCR-08-0098.

PubMed [citation]

PMID:: 18593981

Next-generation sequencing for the diagnosis of hereditary breast and ovarian cancer using genomic capture targeting multiple candidate genes.

Castéra L, Krieger S, Rousselin A, Legros A, Baumann JJ, Bruet O, Brault B, Fouillet R, Goardon N, Letac O, Baert-Desurmont S, Tinat J, Bera O, Dugast C, Berthet P, Polycarpe F, Layet V, Hardouin A, Frébourg T, Vaur D.

Eur J Hum Genet. 2014 Nov;22(11):1305-13. doi: 10.1038/ejhg.2014.16. Epub 2014 Feb 19.

PubMed [citation]

PMID:: 24549055
PMCID:: PMC4200427

See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV000185206.8

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

Description

The c.1142delC pathogenic mutation, located in coding exon 10 of the NBN gene, results from a deletion of one nucleotide at nucleotide position 1142, causing a translational frameshift with a predicted alternate stop codon (p.P381Qfs*23). This alteration has been described in conjunction with a pathogenic founder mutation in at least one patient with Nijmegen breakage syndrome (Varon R et al. Cell. 1998 May;93:467-76). This alteration has also been reported in cohorts of patients with a personal and/or family history of breast and/or ovarian cancers (Walsh T et al. Proc. Natl. Acad. Sci. USA. 2011 Nov;108:18032-7; Castéra L et al. Eur. J. Hum. Genet. 2014 Nov;22:1305-13; Desmond A et al. JAMA Oncol. 2015 Oct;1:943-51; Lu C et al. Nat Commun. 2015 Dec 22;6:10086; Carter NJ et al. Gynecol Oncol. 2018 12;151:481-488). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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: May 12, 2024

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