NM_002485.5(NBN):c.156_157del (p.Ser53fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 28, 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:: RCV000584632.8

Allele description [Variation Report for NM_002485.5(NBN):c.156_157del (p.Ser53fs)]

NM_002485.5(NBN):c.156_157del (p.Ser53fs)

Gene:

NBN:nibrin [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

8q21.3

Genomic location:

Preferred name:

NM_002485.5(NBN):c.156_157del (p.Ser53fs)

HGVS:

NC_000008.10:g.90994964_90994965del
NC_000008.11:g.89982738_89982739del
NG_008860.1:g.6935_6936del
NM_001024688.3:c.-141_-140del
NM_002485.5:c.156_157delMANE SELECT
NP_002476.2:p.Ser53fs
LRG_158:g.6935_6936del
NC_000008.10:g.90994964_90994965del
NC_000008.10:g.90994964_90994965delAA
NC_000008.10:g.90994966_90994967del
NM_002485.4:c.156_157delTT
NM_002485.5:c.156_157del

Links:

dbSNP: rs767454740

NCBI 1000 Genomes Browser:

rs767454740

Molecular consequence:

NM_001024688.3:c.-141_-140del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_002485.5:c.156_157del - 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
SCV001172585	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Mar 28, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24549055, 34072463 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001172585

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Mar 28, 2022)

germline

clinical testing

PubMed (2)
[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

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

Detecting Variants in the NBN Gene While Testing for Hereditary Breast Cancer: What to Do Next?

Zuntini R, Bonora E, Pradella LM, Amato LB, Vidone M, De Fanti S, Catucci I, Cortesi L, Medici V, Ferrari S, Gasparre G, Peterlongo P, Sazzini M, Turchetti D.

Int J Mol Sci. 2021 May 29;22(11). doi:pii: 5832. 10.3390/ijms22115832. Review.

PubMed [citation]

PMID:: 34072463
PMCID:: PMC8198239

Details of each submission

From Ambry Genetics, SCV001172585.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The c.156_157delTT pathogenic mutation, located in coding exon 2 of the NBN gene, results from a deletion of two nucleotides between nucleotide positions 156 and 157, causing a translational frameshift with a predicted alternate stop codon (p.S53Cfs*9). This deletion has been reported in one high risk breast and/or ovarian cancer individual (Castéra L et al. Eur. J. Hum. Genet. 2014 Nov;22:1305-13). (Hu C et al. JAMA, 2018 06;319:2401-2409). (Byrjalsen A et al. PLoS Genet, 2020 12;16:e1009231). (Zuntini R et al. Int J Mol Sci, 2021 May;22:). 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: Jun 2, 2024

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