NM_002485.5(NBN):c.511A>G (p.Ile171Val) AND Hereditary cancer-predisposing syndrome

Germline classification:: Conflicting interpretations of pathogenicity (5 submissions)
Last evaluated:: Jan 24, 2022
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:: RCV000115797.19

Allele description [Variation Report for NM_002485.5(NBN):c.511A>G (p.Ile171Val)]

NM_002485.5(NBN):c.511A>G (p.Ile171Val)

Gene:

NBN:nibrin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q21.3

Genomic location:

Preferred name:

NM_002485.5(NBN):c.511A>G (p.Ile171Val)

Other names:

p.I171V:ATT>GTT

HGVS:

NC_000008.11:g.89978293T>C
NG_008860.1:g.11379A>G
NM_001024688.3:c.265A>G
NM_002485.5:c.511A>GMANE SELECT
NP_001019859.1:p.Ile89Val
NP_002476.2:p.Ile171Val
NP_002476.2:p.Ile171Val
LRG_158t1:c.511A>G
LRG_158:g.11379A>G
LRG_158p1:p.Ile171Val
NC_000008.10:g.90990521T>C
NM_001024688.2:c.265A>G
NM_002485.4:c.511A>G
O60934:p.Ile171Val
p.I171V

Protein change:

I171V; ILE171VAL

Links:

UniProtKB: O60934#VAR_025796; OMIM: 602667.0007; dbSNP: rs61754966

NCBI 1000 Genomes Browser:

rs61754966

Molecular consequence:

NM_001024688.3:c.265A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_002485.5:c.511A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000186698	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Likely benign (Jan 24, 2022)	germline	clinical testing	PubMed (15) [See all records that cite these PMIDs] 11325820, 15338273, 16474176, 18049891, 19452044, 21698754, 22131123, 22373003, 24093751, 24113799, 24830725, 25712764, 26083025, 26722329, 28261280 Citation Link,
SCV000680449	GeneID Lab - Advanced Molecular Diagnostics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 7, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000822086	GeneKor MSA	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 1, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001482298	Department of Pediatric Oncology, Hematology and Clinical Immunology, University Clinics Duesseldorf	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance	maternal	research	PubMed (1) [See all records that cite this PMID]
SCV002536691	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Likely benign (Apr 20, 2021)	germline	curation	Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	maternal	yes	1	not provided	not provided	1	no	research
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	1	not provided	clinical testing, curation
Caucasian	germline	no	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in the Nijmegen Breakage Syndrome gene (NBS1) in childhood acute lymphoblastic leukemia (ALL).

Varon R, Reis A, Henze G, von Einsiedel HG, Sperling K, Seeger K.

Cancer Res. 2001 May 1;61(9):3570-2.

PubMed [citation]

PMID:: 11325820

First case of aplastic anemia in a Japanese child with a homozygous missense mutation in the NBS1 gene (I171V) associated with genomic instability.

Shimada H, Shimizu K, Mimaki S, Sakiyama T, Mori T, Shimasaki N, Yokota J, Nakachi K, Ohta T, Ohki M.

Hum Genet. 2004 Oct;115(5):372-6. Epub 2004 Aug 24.

PubMed [citation]

PMID:: 15338273

See all PubMed Citations (16)

Details of each submission

From Ambry Genetics, SCV000186698.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (15)

Description

This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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

From GeneID Lab - Advanced Molecular Diagnostics, SCV000680449.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Caucasian	1	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	no	not provided	not provided	not provided		1	not provided	not provided	not provided

From GeneKor MSA, SCV000822086.1

#	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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Department of Pediatric Oncology, Hematology and Clinical Immunology, University Clinics Duesseldorf, SCV001482298.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	no	research	PubMed (1)

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

From Sema4, Sema4, SCV002536691.1

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

Last Updated: Apr 15, 2024

ClinVar

Relating variation to medicine