ClinVar Genomic variation as it relates to human health
NM_002485.5(NBN):c.156_157del (p.Ser53fs)
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.156_157del (p.Ser53fs)
Variation ID: 371121 Accession: VCV000371121.30
- Type and length
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Deletion, 2 bp
- Location
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Cytogenetic: 8q21.3 8: 89982736-89982737 (GRCh38) [ NCBI UCSC ] 8: 90994964-90994965 (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 Jan 9, 2017 Feb 20, 2024 Dec 18, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_002485.5:c.156_157del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_002476.2:p.Ser53fs frameshift NM_001024688.3:c.-141_-140del 5 prime UTR NM_002485.4:c.156_157delTT NC_000008.11:g.89982738_89982739del NC_000008.10:g.90994966_90994967del NG_008860.1:g.6935_6936del LRG_158:g.6935_6936del - Protein change
- Other names
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- Canonical SPDI
- NC_000008.11:89982735:AAAA:AA
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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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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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 |
3346 | 3516 |
Conditions - Germline
Condition
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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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Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Dec 18, 2023 | RCV000410370.15 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Sep 12, 2016 | RCV000502852.7 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 28, 2022 | RCV000584632.7 | |
Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Oct 26, 2021 | RCV000484600.8 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Apr 11, 2016 | RCV000587195.3 | |
Pathogenic (1) |
criteria provided, single submitter
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Jun 26, 2021 | RCV002252110.3 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 31, 2022 | RCV002502428.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Aug 23, 2023 | RCV003470344.1 |
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
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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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Likely pathogenic
(Sep 12, 2016)
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criteria provided, single submitter
Method: clinical testing
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Leukemia, acute lymphoblastic
Affected status: yes
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000595917.1
First in ClinVar: Aug 28, 2017 Last updated: Aug 28, 2017 |
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Likely pathogenic
(Apr 11, 2016)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000697948.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
Comment:
Variant summary: The variant of interest causes a frameshift mutation resulting in a predicted truncated NBN protein, a mechanism for disease. The variant of interest … (more)
Variant summary: The variant of interest causes a frameshift mutation resulting in a predicted truncated NBN protein, a mechanism for disease. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 1/121384, which does not exceed the predicted maximum expected allele frequency for a pathogenic NBN variant of 1/8000 for HBOC. The variant of interest has been reported in an affected individual via a publication that consisted of a cohort of HBOC individuals. The variant of interest has not been reported in clinical laboratories or databases. Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as Likely Pathogenic. (less)
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Pathogenic
(Sep 18, 2020)
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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: SCV002046233.1
First in ClinVar: Jan 03, 2022 Last updated: Jan 03, 2022 |
Comment:
This frameshift variant causes the premature termination of NBN protein synthesis. It has been reported in individuals affected with hereditary breast and/or ovarian cancer in … (more)
This frameshift variant causes the premature termination of NBN protein synthesis. It has been reported in individuals affected with hereditary breast and/or ovarian cancer in the published literature (PMID: 24549055 (2014)). Therefore, the variant is classified as pathogenic. (less)
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Pathogenic
(Nov 07, 2021)
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criteria provided, single submitter
Method: clinical testing
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Microcephaly, normal intelligence and immunodeficiency
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002045379.1
First in ClinVar: Jan 03, 2022 Last updated: Jan 03, 2022 |
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Pathogenic
(Jun 26, 2021)
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criteria provided, single submitter
Method: clinical testing
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See cases
Affected status: yes
Allele origin:
germline
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Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein
Accession: SCV002522770.1
First in ClinVar: Jun 09, 2022 Last updated: Jun 09, 2022 |
Comment:
ACMG classification criteria: PVS1, PS4, PM2
Clinical Features:
Seizure (present) , Periventricular leukomalacia (present) , Neurodevelopmental abnormality (present) , Autistic behavior (present) , Aplasia/Hypoplasia of the optic tract (present) , Absent septum pellucidum … (more)
Seizure (present) , Periventricular leukomalacia (present) , Neurodevelopmental abnormality (present) , Autistic behavior (present) , Aplasia/Hypoplasia of the optic tract (present) , Absent septum pellucidum (present) , Abnormal pituitary gland morphology (present) (less)
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Pathogenic
(Mar 28, 2022)
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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: SCV001172585.3
First in ClinVar: Mar 16, 2020 Last updated: Nov 29, 2022 |
Comment:
The c.156_157delTT pathogenic mutation, located in coding exon 2 of the NBN gene, results from a deletion of two nucleotides between nucleotide positions 156 and … (more)
The c.156_157delTT pathogenic mutation, located in coding exon 2 of the NBN gene, results from a deletion of two nucleotides between nucleotide positions 156 and 157, causing a translational frameshift with a predicted alternate stop codon (p.S53Cfs*9). This deletion has been reported in one high risk breast and/or ovarian cancer individual (Castéra L et al. Eur. J. Hum. Genet. 2014 Nov;22:1305-13). (Hu C et al. JAMA, 2018 06;319:2401-2409). (Byrjalsen A et al. PLoS Genet, 2020 12;16:e1009231). (Zuntini R et al. Int J Mol Sci, 2021 May;22:). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
Number of individuals with the variant: 1
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Pathogenic
(Jul 02, 2018)
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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:
unknown
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Mendelics
Accession: SCV000838320.2
First in ClinVar: Oct 10, 2018 Last updated: Dec 11, 2022 |
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Likely pathogenic
(Jul 07, 2016)
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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:
unknown
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Counsyl
Accession: SCV000486614.2
First in ClinVar: Jan 09, 2017 Last updated: Dec 24, 2022 |
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Pathogenic
(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: SCV002810496.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Likely pathogenic
(Oct 26, 2021)
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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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GeneDx
Accession: SCV000568560.6
First in ClinVar: Apr 27, 2017 Last updated: Mar 04, 2023 |
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not … (more)
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek 2016); Observed in an individual with a personal and/or family history of breast and/or ovarian cancer (Castera 2014); This variant is associated with the following publications: (PMID: 29922827, 24549055, 31263571) (less)
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Pathogenic
(Aug 23, 2023)
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criteria provided, single submitter
Method: clinical testing
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Aplastic anemia
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004199597.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Dec 18, 2023)
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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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Invitae
Accession: SCV000553052.9
First in ClinVar: Jan 09, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Ser53Cysfs*9) in the NBN gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Ser53Cysfs*9) in the NBN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NBN are known to be pathogenic (PMID: 9590180, 16415040). This variant is present in population databases (rs767454740, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with hereditary breast and/or ovarian cancer (PMID: 24549055). ClinVar contains an entry for this variant (Variation ID: 371121). For these reasons, this variant has been classified as Pathogenic. (less)
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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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Detecting Variants in the NBN Gene While Testing for Hereditary Breast Cancer: What to Do Next? | Zuntini R | International journal of molecular sciences | 2021 | PMID: 34072463 |
Heterozygous germline mutations in NBS1 among Korean patients with high-risk breast cancer negative for BRCA1/2 mutation. | Kim H | Familial cancer | 2015 | PMID: 25712764 |
Next-generation sequencing for the diagnosis of hereditary breast and ovarian cancer using genomic capture targeting multiple candidate genes. | Castéra L | European journal of human genetics : EJHG | 2014 | PMID: 24549055 |
Mild Nijmegen breakage syndrome phenotype due to alternative splicing. | Varon R | Human molecular genetics | 2006 | PMID: 16415040 |
Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome. | Varon R | Cell | 1998 | PMID: 9590180 |
Text-mined citations for rs767454740 ...
HelpRecord last updated Feb 28, 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.