NM_002485.5(NBN):c.425A>G (p.Asn142Ser) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely benign (2 submissions)
Last evaluated:: Oct 19, 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:: RCV000115794.15

Allele description [Variation Report for NM_002485.5(NBN):c.425A>G (p.Asn142Ser)]

NM_002485.5(NBN):c.425A>G (p.Asn142Ser)

Gene:

NBN:nibrin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q21.3

Genomic location:

Preferred name:

NM_002485.5(NBN):c.425A>G (p.Asn142Ser)

Other names:

p.N142S:AAT>AGT

HGVS:

NC_000008.11:g.89980789T>C
NG_008860.1:g.8883A>G
NM_001024688.3:c.179A>G
NM_002485.5:c.425A>GMANE SELECT
NP_001019859.1:p.Asn60Ser
NP_002476.2:p.Asn142Ser
NP_002476.2:p.Asn142Ser
LRG_158t1:c.425A>G
LRG_158:g.8883A>G
LRG_158p1:p.Asn142Ser
NC_000008.10:g.90993017T>C
NM_002485.4:c.425A>G
O60934:p.Asn142Ser
p.N142S

Protein change:

N142S; Asn142Ser

Links:

UniProtKB: O60934#VAR_051226; dbSNP: rs769414

NCBI 1000 Genomes Browser:

rs769414

Molecular consequence:

NM_001024688.3:c.179A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_002485.5:c.425A>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
SCV000186535	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Oct 19, 2021)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 12376507, 12427538, 24728327, 24894818, 26315354, 26787654, 28873162, 29758565, 31206626 Citation Link,
SCV002536680	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Likely benign (Jun 21, 2021)	germline	curation	PubMed (3) [See all records that cite these PMIDs] 26315354, 28873162, 24894818 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000186535

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(Oct 19, 2021)

germline

clinical testing

PubMed (9)
[See all records that cite these PMIDs]

Citation Link,

SCV002536680

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Likely benign
(Jun 21, 2021)

germline

curation

PubMed (3)
[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, curation

Citations

PubMed

Identification of 127 amino acid substitution variants in screening 37 DNA repair genes in humans.

Mohrenweiser HW, Xi T, Vázquez-Matías J, Jones IM.

Cancer Epidemiol Biomarkers Prev. 2002 Oct;11(10 Pt 1):1054-64.

PubMed [citation]

PMID:: 12376507

Coding variants in human double-strand break DNA repair genes.

Ruttan CC, Glickman BW.

Mutat Res. 2002 Nov 30;509(1-2):175-200.

PubMed [citation]

PMID:: 12427538

See all PubMed Citations (9)

Details of each submission

From Ambry Genetics, SCV000186535.8

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

Description

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Sema4, Sema4, SCV002536680.1

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

#	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: May 7, 2024

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