NM_002485.5(NBN):c.284A>G (p.Asp95Gly) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 12, 2023
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:: RCV000130482.12

Allele description [Variation Report for NM_002485.5(NBN):c.284A>G (p.Asp95Gly)]

NM_002485.5(NBN):c.284A>G (p.Asp95Gly)

Gene:

NBN:nibrin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q21.3

Genomic location:

Preferred name:

NM_002485.5(NBN):c.284A>G (p.Asp95Gly)

HGVS:

NC_000008.11:g.89981411T>C
NG_008860.1:g.8261A>G
NM_001024688.3:c.38A>G
NM_002485.5:c.284A>GMANE SELECT
NP_001019859.1:p.Asp13Gly
NP_002476.2:p.Asp95Gly
NP_002476.2:p.Asp95Gly
LRG_158t1:c.284A>G
LRG_158:g.8261A>G
LRG_158p1:p.Asp95Gly
NC_000008.10:g.90993639T>C
NM_002485.4:c.284A>G
p.D95G

Protein change:

D13G

Links:

dbSNP: rs545276922

NCBI 1000 Genomes Browser:

rs545276922

Molecular consequence:

NM_001024688.3:c.38A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_002485.5:c.284A>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000185351	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jan 12, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29522266, 33471991 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000185351

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jan 12, 2023)

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

Gene panel testing of 5589 BRCA1/2-negative index patients with breast cancer in a routine diagnostic setting: results of the German Consortium for Hereditary Breast and Ovarian Cancer.

Hauke J, Horvath J, Groß E, Gehrig A, Honisch E, Hackmann K, Schmidt G, Arnold N, Faust U, Sutter C, Hentschel J, Wang-Gohrke S, Smogavec M, Weber BHF, Weber-Lassalle N, Weber-Lassalle K, Borde J, Ernst C, Altmüller J, Volk AE, Thiele H, Hübbel V, et al.

Cancer Med. 2018 Apr;7(4):1349-1358. doi: 10.1002/cam4.1376. Epub 2018 Mar 9.

PubMed [citation]

PMID:: 29522266
PMCID:: PMC5911592

Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.

Breast Cancer Association Consortium., Dorling L, Carvalho S, Allen J, González-Neira A, Luccarini C, Wahlström C, Pooley KA, Parsons MT, Fortuno C, Wang Q, Bolla MK, Dennis J, Keeman R, Alonso MR, Álvarez N, Herraez B, Fernandez V, Núñez-Torres R, Osorio A, Valcich J, Li M, et al.

N Engl J Med. 2021 Feb 4;384(5):428-439. doi: 10.1056/NEJMoa1913948. Epub 2021 Jan 20.

PubMed [citation]

PMID:: 33471991
PMCID:: PMC7611105

Details of each submission

From Ambry Genetics, SCV000185351.9

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

Description

The p.D95G variant (also known as c.284A>G), located in coding exon 3 of the NBN gene, results from an A to G substitution at nucleotide position 284. The aspartic acid at codon 95 is replaced by glycine, an amino acid with similar properties. This alteration was detected in 2/5589 German BRCA1/2-negative probands with breast cancer (Hauke J et al. Cancer Med, 2018 Apr;7:1349-1358). This variant was reported in 17/60,466 breast cancer cases and in 5/53,461 controls (Dorling et al. N Engl J Med. 2021 02;384:428-439). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious 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: Jun 17, 2024

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