NM_002485.5(NBN):c.1509T>G (p.Asn503Lys) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 24, 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:: RCV000565151.9

Allele description [Variation Report for NM_002485.5(NBN):c.1509T>G (p.Asn503Lys)]

NM_002485.5(NBN):c.1509T>G (p.Asn503Lys)

Gene:

NBN:nibrin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q21.3

Genomic location:

Preferred name:

NM_002485.5(NBN):c.1509T>G (p.Asn503Lys)

HGVS:

NC_000008.11:g.89953580A>C
NG_008860.1:g.36092T>G
NM_001024688.3:c.1263T>G
NM_002485.5:c.1509T>GMANE SELECT
NP_001019859.1:p.Asn421Lys
NP_002476.2:p.Asn503Lys
NP_002476.2:p.Asn503Lys
LRG_158t1:c.1509T>G
LRG_158:g.36092T>G
LRG_158p1:p.Asn503Lys
NC_000008.10:g.90965808A>C
NM_002485.4:c.1509T>G

Protein change:

N421K

Links:

dbSNP: rs876660751

NCBI 1000 Genomes Browser:

rs876660751

Molecular consequence:

NM_001024688.3:c.1263T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_002485.5:c.1509T>G - missense variant - [Sequence Ontology: SO:0001583]

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

Recent activity

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Mus musculus pituitary homeobox 2 isoform a (Pitx2) mRNA, complete cds
Mus musculus pituitary homeobox 2 isoform a (Pitx2) mRNA, complete cds
gi|1930007|gb|U80011.1|MMU80011

Nucleotide
Mus musculus orthodenticle-like homeobox 2 (Otlx2) mRNA, complete cds
Mus musculus orthodenticle-like homeobox 2 (Otlx2) mRNA, complete cds
gi|1724115|gb|U80036.1|MMU80036

Nucleotide
Homo sapiens acetyl-CoA carboxylase beta (ACACB), transcript variant 4, mRNA
Homo sapiens acetyl-CoA carboxylase beta (ACACB), transcript variant 4, mRNA
gi|2318375358|ref|NM_001412736.1|

Nucleotide
uncharacterized protein LOC111437167 [Cucurbita moschata]
uncharacterized protein LOC111437167 [Cucurbita moschata]
gi|1279840584|ref|XP_022930792.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000662683	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Aug 24, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24894818, 26787654 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000662683

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Aug 24, 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

Rare key functional domain missense substitutions in MRE11A, RAD50, and NBN contribute to breast cancer susceptibility: results from a Breast Cancer Family Registry case-control mutation-screening study.

Damiola F, Pertesi M, Oliver J, Le Calvez-Kelm F, Voegele C, Young EL, Robinot N, Forey N, Durand G, Vallée MP, Tao K, Roane TC, Williams GJ, Hopper JL, Southey MC, Andrulis IL, John EM, Goldgar DE, Lesueur F, Tavtigian SV.

Breast Cancer Res. 2014 Jun 3;16(3):R58. doi: 10.1186/bcr3669.

PubMed [citation]

PMID:: 24894818
PMCID:: PMC4229874

Multigene testing of moderate-risk genes: be mindful of the missense.

Young EL, Feng BJ, Stark AW, Damiola F, Durand G, Forey N, Francy TC, Gammon A, Kohlmann WK, Kaphingst KA, McKay-Chopin S, Nguyen-Dumont T, Oliver J, Paquette AM, Pertesi M, Robinot N, Rosenthal JS, Vallee M, Voegele C, Hopper JL, Southey MC, Andrulis IL, et al.

J Med Genet. 2016 Jun;53(6):366-76. doi: 10.1136/jmedgenet-2015-103398. Epub 2016 Jan 19.

PubMed [citation]

PMID:: 26787654
PMCID:: PMC4893078

Details of each submission

From Ambry Genetics, SCV000662683.5

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

Description

The p.N503K variant (also known as c.1509T>G), located in coding exon 11 of the NBN gene, results from a T to G substitution at nucleotide position 1509. The asparagine at codon 503 is replaced by lysine, an amino acid with similar properties. This alteration was reported in a study of 1297 cases of early-onset breast cancer and 1121 controls (Young EL et al. J. Med. Genet., 2016 06;53:366-76). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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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