NM_002485.5(NBN):c.156_157del (p.Ser53fs) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Oct 26, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000484600.8

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)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000568560	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Oct 26, 2021)	germline	clinical testing	Citation Link,
SCV002046233	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Sep 18, 2020)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 24549055, 25712764, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000568560

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Oct 26, 2021)

germline

clinical testing

Citation Link,

SCV002046233

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(Sep 18, 2020)

unknown

clinical testing

PubMed (3)
[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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	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

Heterozygous germline mutations in NBS1 among Korean patients with high-risk breast cancer negative for BRCA1/2 mutation.

Kim H, Cho DY, Choi DH, Jung GH, Shin I, Park W, Huh SJ, Kim SW, Park SK, Lee JW, Nam SJ, Lee JE, Gil WH, Kim SW.

Fam Cancer. 2015 Sep;14(3):365-71. doi: 10.1007/s10689-015-9789-9.

PubMed [citation]

PMID:: 25712764

See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000568560.6

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

Description

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek 2016); Observed in an individual with a personal and/or family history of breast and/or ovarian cancer (Castera 2014); This variant is associated with the following publications: (PMID: 29922827, 24549055, 31263571)

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV002046233.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This frameshift variant causes the premature termination of NBN protein synthesis. It has been reported in individuals affected with hereditary breast and/or ovarian cancer in the published literature (PMID: 24549055 (2014)). Therefore, the variant is classified as pathogenic.

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

Last Updated: Jun 2, 2024

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