ClinVar Genomic variation as it relates to human health
NM_002485.5(NBN):c.1882G>A (p.Glu628Lys)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_002485.5(NBN):c.1882G>A (p.Glu628Lys)
Variation ID: 132690 Accession: VCV000132690.44
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 8q21.3 8: 89947856 (GRCh38) [ NCBI UCSC ] 8: 90960084 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jun 1, 2016 Oct 20, 2024 Jan 29, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_002485.5:c.1882G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_002476.2:p.Glu628Lys missense NM_001024688.3:c.1636G>A NP_001019859.1:p.Glu546Lys missense NC_000008.11:g.89947856C>T NC_000008.10:g.90960084C>T NG_008860.1:g.41816G>A LRG_158:g.41816G>A LRG_158t1:c.1882G>A LRG_158p1:p.Glu628Lys - Protein change
- E628K, E546K
- Other names
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p.E628K:GAA>AAA
NP_002476.2:p.Glu628Lys
- Canonical SPDI
- NC_000008.11:89947855:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.00419 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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The Genome Aggregation Database (gnomAD), exomes 0.00090
Exome Aggregation Consortium (ExAC) 0.00186
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00347
1000 Genomes Project 0.00419
Trans-Omics for Precision Medicine (TOPMed) 0.00482
1000 Genomes Project 30x 0.00422
The Genome Aggregation Database (gnomAD) 0.00466
- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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NBN | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
3420 | 3593 | |
LOC126860438 | - | - | - | GRCh38 | - | 145 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Benign (2) |
criteria provided, multiple submitters, no conflicts
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Jul 23, 2015 | RCV000131006.17 | |
Benign (5) |
criteria provided, multiple submitters, no conflicts
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Apr 24, 2021 | RCV000212752.21 | |
Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
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Sep 1, 2023 | RCV000224857.31 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
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Jan 29, 2024 | RCV001084223.20 | |
Benign (1) |
criteria provided, single submitter
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Jul 7, 2023 | RCV003315700.8 | |
Likely benign (1) |
criteria provided, single submitter
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Apr 19, 2022 | RCV002225345.9 | |
Likely benign (1) |
criteria provided, single submitter
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Mar 31, 2022 | RCV002498542.8 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Benign
(Jan 02, 2014)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000170642.11
First in ClinVar: Jun 23, 2014 Last updated: Jun 01, 2016 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
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Benign
(Jul 23, 2015)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000685740.2
First in ClinVar: Feb 19, 2018 Last updated: Dec 11, 2022 |
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Likely Benign
(Dec 22, 2015)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
|
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Accession: SCV000281644.1
First in ClinVar: Jun 08, 2016 Last updated: Jun 08, 2016 |
Comment:
Converted during submission to Likely benign.
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Benign
(Nov 22, 2016)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000806420.1
First in ClinVar: Sep 13, 2018 Last updated: Sep 13, 2018 |
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Likely benign
(Aug 22, 2019)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001471633.1
First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021 |
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Benign
(Apr 24, 2021)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000697957.2
First in ClinVar: Jun 08, 2016 Last updated: May 21, 2021 |
Comment:
Variant summary: NBN c.1882G>A (p.Glu628Lys) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign … (more)
Variant summary: NBN c.1882G>A (p.Glu628Lys) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00088 in 241282 control chromosomes, predominantly at a frequency of 0.012 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 96 fold of the estimated maximal expected allele frequency for a pathogenic variant in NBN causing Hereditary Breast And Ovarian Cancer Syndrome phenotype (0.00013), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.1882G>A has been reported in the literature in individuals who underwent testing for Hereditary Breast and Ovarian Cancer and/or Lynch Syndrome, without strong evidence for causality (examples- Haiman_2013, Yorczyk_2015, Yurgelun_2015, Tung_2015). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Eight clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign (n=5)/likely benign (n=3). Based on the evidence outlined above, the variant was classified as benign. (less)
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Likely benign
(Apr 19, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
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National Health Laboratory Service, Universitas Academic Hospital and University of the Free State
Accession: SCV002505285.1
First in ClinVar: Apr 30, 2022 Last updated: Apr 30, 2022 |
Number of individuals with the variant: 17
Geographic origin: South Africa
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Likely benign
(Mar 31, 2022)
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criteria provided, single submitter
Method: clinical testing
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Microcephaly, normal intelligence and immunodeficiency
Aplastic anemia Acute lymphoid leukemia
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002810597.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Benign
(Jul 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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Acute lymphoid leukemia
Affected status: yes
Allele origin:
germline
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KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV004016050.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
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Benign
(Aug 15, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000888329.4
First in ClinVar: Jun 08, 2016 Last updated: Jan 06, 2024 |
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Benign
(Jan 29, 2024)
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criteria provided, single submitter
Method: clinical testing
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Microcephaly, normal intelligence and immunodeficiency
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000153825.14
First in ClinVar: Jun 03, 2014 Last updated: Feb 28, 2024 |
|
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Benign
(Dec 02, 2014)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000185932.8
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as 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. (less)
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Benign
(Apr 28, 2017)
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criteria provided, single submitter
Method: clinical testing
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Microcephaly, normal intelligence and immunodeficiency
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001324784.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. (less)
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Likely benign
(Sep 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV004155987.10
First in ClinVar: Nov 20, 2023 Last updated: Oct 20, 2024 |
Comment:
NBN: BP4, BS1
Number of individuals with the variant: 1
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001930305.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001972622.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, Amsterdam University Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001977792.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. | Breast Cancer Association Consortium | The New England journal of medicine | 2021 | PMID: 33471991 |
Germline Mutations in the BRIP1, BARD1, PALB2, and NBN Genes in Women With Ovarian Cancer. | Ramus SJ | Journal of the National Cancer Institute | 2015 | PMID: 26315354 |
Identification of a Variety of Mutations in Cancer Predisposition Genes in Patients With Suspected Lynch Syndrome. | Yurgelun MB | Gastroenterology | 2015 | PMID: 25980754 |
Use of panel tests in place of single gene tests in the cancer genetics clinic. | Yorczyk A | Clinical genetics | 2015 | PMID: 25318351 |
Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel. | Tung N | Cancer | 2015 | PMID: 25186627 |
Genome-wide testing of putative functional exonic variants in relationship with breast and prostate cancer risk in a multiethnic population. | Haiman CA | PLoS genetics | 2013 | PMID: 23555315 |
Text-mined citations for rs115321485 ...
HelpRecord last updated Nov 10, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.