NM_002485.5(NBN):c.1690G>A (p.Glu564Lys) AND not provided

Germline classification:: Benign/Likely benign (4 submissions)
Last evaluated:: Mar 1, 2024
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:: RCV000589500.32

Allele description [Variation Report for NM_002485.5(NBN):c.1690G>A (p.Glu564Lys)]

NM_002485.5(NBN):c.1690G>A (p.Glu564Lys)

Gene:

NBN:nibrin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q21.3

Genomic location:

Preferred name:

NM_002485.5(NBN):c.1690G>A (p.Glu564Lys)

Other names:

p.E564K:GAA>AAA

HGVS:

NC_000008.11:g.89953399C>T
NG_008860.1:g.36273G>A
NM_001024688.3:c.1444G>A
NM_002485.5:c.1690G>AMANE SELECT
NP_001019859.1:p.Glu482Lys
NP_002476.2:p.Glu564Lys
NP_002476.2:p.Glu564Lys
LRG_158t1:c.1690G>A
LRG_158:g.36273G>A
LRG_158p1:p.Glu564Lys
NC_000008.10:g.90965627C>T
NM_002485.4:c.1690G>A
p.E564K

Protein change:

E482K

Links:

dbSNP: rs72550742

NCBI 1000 Genomes Browser:

rs72550742

Molecular consequence:

NM_001024688.3:c.1444G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002485.5:c.1690G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Slc29a3 solute carrier family 29 (nucleoside transporters), member 3 [Mus muscul...
Slc29a3 solute carrier family 29 (nucleoside transporters), member 3 [Mus musculus]
Gene ID:71279

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000697949	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Mar 21, 2016)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 25712764, 24349281, 25980754, 26315354 LabCorp Variant Classification Summary - May 2015.docx, Citation Link,
SCV000888326	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Benign (Jun 19, 2023)	unknown	clinical testing	PubMed (9) [See all records that cite these PMIDs] 28135145, 30287823, 29929473, 24349281, 26315354, 25980754, 25712764, 26976419, 26467025
SCV001245907	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Likely benign (Mar 1, 2024)	germline	clinical testing	Citation Link,
SCV005221698	Breakthrough Genomics, Breakthrough Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign	germline	not provided	PubMed (1) [See all records that cite this PMID]

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
not provided	germline	yes	2	not provided	not provided	not provided	not provided	clinical testing, not provided
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Cancer Susceptibility Gene Mutations in Individuals With Colorectal Cancer.

Yurgelun MB, Kulke MH, Fuchs CS, Allen BA, Uno H, Hornick JL, Ukaegbu CI, Brais LK, McNamara PG, Mayer RJ, Schrag D, Meyerhardt JA, Ng K, Kidd J, Singh N, Hartman AR, Wenstrup RJ, Syngal S.

J Clin Oncol. 2017 Apr 1;35(10):1086-1095. doi: 10.1200/JCO.2016.71.0012. Epub 2017 Jan 30.

PubMed [citation]

PMID:: 28135145
PMCID:: PMC5455355

Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls.

Momozawa Y, Iwasaki Y, Parsons MT, Kamatani Y, Takahashi A, Tamura C, Katagiri T, Yoshida T, Nakamura S, Sugano K, Miki Y, Hirata M, Matsuda K, Spurdle AB, Kubo M.

Nat Commun. 2018 Oct 4;9(1):4083. doi: 10.1038/s41467-018-06581-8.

PubMed [citation]

PMID:: 30287823
PMCID:: PMC6172276

See all PubMed Citations (10)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000697949.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

Variant summary: The NBN c.1690G>A variant affects a conserved nucleotide, resulting in amino acid change from Glu to Lys. 3/4 in-silico tools predict this variant to be benign (SNPs&GO not captured due to low reliability index). Functional studies have not been carried out to prove or disprove these in silico predictions. The variant of interest was observed in a large, broad control population, ExAC, with an allele frequency of 118/121386 (1/1028), predominantly found in the East Asian cohort, 91/8654 (1/95), which exceeds the predicted maximum expected allele frequency for a pathogenic NBN variant of 1/8000 for HBOC. Therefore, suggesting that the variant of interest is a common polymorphism found in population(s) of East Asian origin. The variant has also been cited in cancer patients of East Asian origin, but without evidence of causality (i.e. co-segregation data). In addition, several clinical laboratories classified this variant as benign/likely benign. Taken together, the variant of interest was 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 Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000888326.4

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

#	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 CeGaT Center for Human Genetics Tuebingen, SCV001245907.26

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	not provided

Description

NBN: BP4, 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		2	not provided	not provided	not provided

From Breakthrough Genomics, Breakthrough Genomics, SCV005221698.1

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

Last Updated: Oct 20, 2024

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