NM_002485.5(NBN):c.283G>A (p.Asp95Asn) AND not provided

Germline classification:: Conflicting classifications of pathogenicity (8 submissions)
Last evaluated:: Jun 1, 2025
Review status:: criteria provided, conflicting classifications

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:: RCV000588621.59

Allele description [Variation Report for NM_002485.5(NBN):c.283G>A (p.Asp95Asn)]

NM_002485.5(NBN):c.283G>A (p.Asp95Asn)

Gene:

NBN:nibrin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q21.3

Genomic location:

Preferred name:

NM_002485.5(NBN):c.283G>A (p.Asp95Asn)

Other names:

p.D95N:GAT>AAT

HGVS:

NC_000008.11:g.89981412C>T
NG_008860.1:g.8260G>A
NM_001024688.3:c.37G>A
NM_002485.5:c.283G>AMANE SELECT
NP_001019859.1:p.Asp13Asn
NP_002476.2:p.Asp95Asn
NP_002476.2:p.Asp95Asn
LRG_158t1:c.283G>A
LRG_158:g.8260G>A
LRG_158p1:p.Asp95Asn
NC_000008.10:g.90993640C>T
NM_002485.4:c.283G>A
O60934:p.Asp95Asn
p.D95N

Protein change:

D13N

Links:

UniProtKB: O60934#VAR_025793; dbSNP: rs61753720

NCBI 1000 Genomes Browser:

rs61753720

Molecular consequence:

NM_001024688.3:c.37G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002485.5:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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
SCV000601688	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Benign (Aug 2, 2019)	unknown	clinical testing	PubMed (17) [See all records that cite these PMIDs] 29371908, 16702373, 11325820, 17894553, 26092435, 16810201, 24728327, 24113799, 19523210, 35264596, 35245693, 32522261, 33046446, 32854451, 30995915, 31278556, 26467025
SCV000697966	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Apr 18, 2016)	germline	clinical testing	PubMed (11) [See all records that cite these PMIDs] 24113799, 24728327, 16702373, 23555315, 26315354, 11325820, 14559852, 12679336, 26092435, 16810201, 19523210 LabCorp Variant Classification Summary - May 2015.docx, Citation Link,
SCV000780920	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Likely benign (Jun 1, 2025)	germline	clinical testing	Citation Link,
SCV000806433	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Jun 15, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000885815	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	Benign (Jul 26, 2024)	germline	clinical testing	Citation Link,
SCV001742309	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus	no assertion criteria provided	Likely benign	germline	clinical testing
SCV001806806	Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus	no assertion criteria provided	Likely benign	germline	clinical testing
SCV004224197	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 6, 2022)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 16702373, 16810201, 29371908, 30777372, 32522261, 32854451, 35245693, 35264596, 25741868

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	14	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	2	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Increased risk of larynx cancer in heterozygous carriers of the I171V mutation of the NBS1 gene.

Ziólkowska I, Mosor M, Wierzbicka M, Rydzanicz M, Pernak-Schwarz M, Nowak J.

Cancer Sci. 2007 Nov;98(11):1701-5.

PubMed [citation]

PMID:: 17894553
PMCID:: PMC11158328

High frequency of variants in genes associated with primary immunodeficiencies in patients with rheumatic diseases with secondary hypogammaglobulinaemia.

Sogkas G, Dubrowinskaja N, Adriawan IR, Anim M, Witte T, Schmidt RE, Atschekzei F.

Ann Rheum Dis. 2021 Mar;80(3):392-399. doi: 10.1136/annrheumdis-2020-218280. Epub 2020 Oct 12.

PubMed [citation]

PMID:: 33046446

See all PubMed Citations (23)

Details of each submission

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000601688.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (17)

#	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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000697966.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (11)

Description

Variant summary: The variant of interest causes a missense change involving a conserved nucleotide with 3/4 in silico programs (SNPs&GO not captured here due to low reliability index) predict a "deleterious" outcome. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 225/121130 (1/538), which exceeds the predicted maximum expected allele frequency for a pathogenic NBN variant of 1/8000 for HBOC. The variant of interest has been reported in multiple affected individuals (ALL, OvC, BrC) with limited information ie lack of co-occurrence and co-segregation data. In addition, multiple reputable clinical laboratories cite the variant with a classification of "likely benign/benign." Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as Benign.

#	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

From CeGaT Center for Human Genetics Tuebingen, SCV000780920.35

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	14	not provided	not provided	clinical testing	not provided

Description

NBN: BS1

#	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		14	not provided	not provided	not provided

From PreventionGenetics, part of Exact Sciences, SCV000806433.1

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

#	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

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000885815.6

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

#	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

From Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus, SCV001742309.3

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

#	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 Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus, SCV001806806.1

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

#	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 Mayo Clinic Laboratories, Mayo Clinic, SCV004224197.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (9)

Description

BS1

#	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		2	not provided	not provided	not provided

Last Updated: Jul 13, 2025

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