NM_002485.5(NBN):c.1809C>A (p.Phe603Leu) AND not provided

Germline classification:: Benign/Likely benign (2 submissions)
Last evaluated:: Jan 28, 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:: RCV000589243.9

Allele description [Variation Report for NM_002485.5(NBN):c.1809C>A (p.Phe603Leu)]

NM_002485.5(NBN):c.1809C>A (p.Phe603Leu)

Gene:

NBN:nibrin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q21.3

Genomic location:

Preferred name:

NM_002485.5(NBN):c.1809C>A (p.Phe603Leu)

HGVS:

NC_000008.11:g.89953280G>T
NG_008860.1:g.36392C>A
NM_001024688.3:c.1563C>A
NM_002485.5:c.1809C>AMANE SELECT
NP_001019859.1:p.Phe521Leu
NP_002476.2:p.Phe603Leu
NP_002476.2:p.Phe603Leu
LRG_158t1:c.1809C>A
LRG_158:g.36392C>A
LRG_158p1:p.Phe603Leu
NC_000008.10:g.90965508G>T
NM_002485.4:c.1809C>A
p.F603L

Protein change:

F521L

Links:

dbSNP: rs192236678

NCBI 1000 Genomes Browser:

rs192236678

Molecular consequence:

NM_001024688.3:c.1563C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002485.5:c.1809C>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000513863	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely benign (Jan 28, 2021)	germline	clinical testing	Citation Link,
SCV000697955	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Jun 5, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25712764, 24349281, 26315354 LabCorp Variant Classification Summary - May 2015.docx Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000513863

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely benign
(Jan 28, 2021)

germline

clinical testing

Citation Link,

SCV000697955

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Benign
(Jun 5, 2017)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Heterozygous germline mutations in NBS1 among Korean patients with high-risk breast cancer negative for BRCA1/2 mutation.

Kim H, Cho DY, Choi DH, Jung GH, Shin I, Park W, Huh SJ, Kim SW, Park SK, Lee JW, Nam SJ, Lee JE, Gil WH, Kim SW.

Fam Cancer. 2015 Sep;14(3):365-71. doi: 10.1007/s10689-015-9789-9.

PubMed [citation]

PMID:: 25712764

Mutation inactivation of Nijmegen breakage syndrome gene (NBS1) in hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

Wang Y, Hong Y, Li M, Long J, Zhao YP, Zhang JX, Li Q, You H, Tong WM, Jia JD, Huang J.

PLoS One. 2013;8(12):e82426. doi: 10.1371/journal.pone.0082426.

PubMed [citation]

PMID:: 24349281
PMCID:: PMC3862623

See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000513863.6

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

Description

This variant is associated with the following publications: (PMID: 24349281, 25712764, 26315354, 23555315, 30942098, 32668560)

#	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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000697955.1

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

Description

Variant summary: The NBN c.1809C>A (p.Phe603Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. 5/5 in silico tools predict a benign outcome for this variant. This variant was found in 40/128334 control chromosomes, predominantly observed in the East Asian subpopulation at a frequency of 0.004161 (36/8652). This frequency is about 33 times the estimated maximal expected allele frequency of a pathogenic NBN variant (0.000125), suggesting this is likely a benign polymorphism found primarily in the populations of East Asian origin. his variant was reported in two studies in non-BRCA1/2 Korean patients with high-risk breast cancer and European populations with high risk of ovarian cancer, but was also observed in controls (Kim_FC_2015, Ramus_NBN1_JNCI_2015). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign/benign. Taken together, this variant 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

Last Updated: Feb 20, 2024

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