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NM_002485.5(NBN):c.2215C>G (p.Leu739Val) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Feb 24, 2023
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:
RCV000160797.15

Allele description [Variation Report for NM_002485.5(NBN):c.2215C>G (p.Leu739Val)]

NM_002485.5(NBN):c.2215C>G (p.Leu739Val)

Gene:
NBN:nibrin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
8q21.3
Genomic location:
Preferred name:
NM_002485.5(NBN):c.2215C>G (p.Leu739Val)
Other names:
p.L739V:CTT>GTT
HGVS:
  • NC_000008.11:g.89937045G>C
  • NG_008860.1:g.52627C>G
  • NM_001024688.3:c.1969C>G
  • NM_002485.5:c.2215C>GMANE SELECT
  • NP_001019859.1:p.Leu657Val
  • NP_002476.2:p.Leu739Val
  • NP_002476.2:p.Leu739Val
  • LRG_158t1:c.2215C>G
  • LRG_158:g.52627C>G
  • LRG_158p1:p.Leu739Val
  • NC_000008.10:g.90949273G>C
  • NM_002485.4:c.2215C>G
  • p.L739V
Protein change:
L657V
Links:
dbSNP: rs370058152
NCBI 1000 Genomes Browser:
rs370058152
Molecular consequence:
  • NM_001024688.3:c.1969C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002485.5:c.2215C>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

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000215461Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Feb 24, 2023) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV002536646Sema4, Sema4
criteria provided, single submitter

(Sema4 Curation Guidelines)		Uncertain significance
(Jun 25, 2021) 		germlinecuration

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing, curation

Citations

PubMed

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

Comprehensive germline-genomic and clinical profiling in 160 unselected children and adolescents with cancer.

Wagener R, Taeubner J, Walter C, Yasin L, Alzoubi D, Bartenhagen C, Attarbaschi A, Classen CF, Kontny U, Hauer J, Fischer U, Dugas M, Kuhlen M, Borkhardt A, Brozou T.

Eur J Hum Genet. 2021 Aug;29(8):1301-1311. doi: 10.1038/s41431-021-00878-x. Epub 2021 Apr 12.

PubMed [citation]
PMID:
33840814
PMCID:
PMC8385053

Details of each submission

From Ambry Genetics, SCV000215461.8

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The p.L739V variant (also known as c.2215C>G), located in coding exon 15 of the NBN gene, results from a C to G substitution at nucleotide position 2215. The leucine at codon 739 is replaced by valine, an amino acid with highly similar properties. This variant was detected in 1/160 children with newly diagnosed cancer. This patient was diagnosed with pilocytic astrocytoma (Wagener R et al. Eur J Hum Genet, 2021 Aug;29:1301-1311). This variant was also reported in 3/60,466 breast cancer cases and in 2/53,461 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 tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Sema4, Sema4, SCV002536646.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024