ClinVar Genomic variation as it relates to human health
NM_002485.5(NBN):c.102G>A (p.Leu34=)
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.102G>A (p.Leu34=)
Variation ID: 183697 Accession: VCV000183697.44
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 8q21.3 8: 89982791 (GRCh38) [ NCBI UCSC ] 8: 90995019 (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 Mar 24, 2015 Sep 29, 2024 Feb 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_002485.5:c.102G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_002476.2:p.Leu34= synonymous NM_001024688.3:c.-195G>A 5 prime UTR NC_000008.11:g.89982791C>T NC_000008.10:g.90995019C>T NG_008860.1:g.6881G>A LRG_158:g.6881G>A LRG_158t1:c.102G>A LRG_158p1:p.Leu34= - Protein change
- Other names
- NP_002476.2:p.Leu34=
- Canonical SPDI
- NC_000008.11:89982790: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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0.37919 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.31316
The Genome Aggregation Database (gnomAD) 0.32752
Trans-Omics for Precision Medicine (TOPMed) 0.32860
Exome Aggregation Consortium (ExAC) 0.35272
The Genome Aggregation Database (gnomAD), exomes 0.35351
1000 Genomes Project 30x 0.37164
1000 Genomes Project 0.37919
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
Help
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 |
3419 | 3592 |
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 (1) |
criteria provided, single submitter
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Nov 18, 2014 | RCV000162359.11 | |
Benign (4) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV000387572.26 | |
Benign (6) |
criteria provided, multiple submitters, no conflicts
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Jan 24, 2024 | RCV000242759.23 | |
Benign (1) |
criteria provided, single submitter
|
Apr 19, 2022 | RCV002225467.9 | |
Benign (1) |
criteria provided, single submitter
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Jul 7, 2023 | RCV003315969.8 | |
Benign (3) |
criteria provided, multiple submitters, no conflicts
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Nov 6, 2023 | RCV001711427.18 |
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
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Microcephaly, normal intelligence and immunodeficiency
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000634194.7
First in ClinVar: Dec 26, 2017 Last updated: Feb 14, 2024 |
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Benign
(Nov 06, 2023)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV002048670.4
First in ClinVar: Jan 08, 2022 Last updated: Feb 20, 2024 |
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Benign
(Mar 03, 2015)
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criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001940516.2
First in ClinVar: Sep 29, 2021 Last updated: Mar 04, 2023 |
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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
|
KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV004016041.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
|
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Benign
(Nov 18, 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
|
Ambry Genetics
Accession: SCV000212662.7
First in ClinVar: Mar 24, 2015 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
(-)
|
criteria provided, single submitter
Method: not provided
|
not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005264908.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
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Benign
(-)
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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: SCV000309094.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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Benign
(Mar 28, 2016)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000539867.2
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
Comment:
Disclaimer: This variant has not undergone full assessment. The following are pr eliminary notes: Frequency
Number of individuals with the variant: 1
|
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Benign
(Jan 13, 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:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000475302.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
|
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Benign
(Jul 01, 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
|
Genome-Nilou Lab
Accession: SCV001748581.1
First in ClinVar: Jul 10, 2021 Last updated: Jul 10, 2021 |
Sex: mixed
|
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Benign
(Apr 19, 2022)
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criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State
Accession: SCV002505319.1
First in ClinVar: Apr 30, 2022 Last updated: Apr 30, 2022 |
Number of individuals with the variant: 173
Geographic origin: South Africa
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Benign
(Jan 24, 2024)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: no
Allele origin:
germline
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Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan
Accession: SCV004233206.1
First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024 |
Comment:
This variant is classified as Benign based on local population frequency. This variant was detected in 63% of patients studied by a panel of primary … (more)
This variant is classified as Benign based on local population frequency. This variant was detected in 63% of patients studied by a panel of primary immunodeficiencies. Number of patients: 60. Only high quality variants are reported. (less)
Number of individuals with the variant: 60
Age: <18 years
Sex: mixed
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001744880.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 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: SCV001971990.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Benign
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Nijmegen breakage syndrome
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001461785.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 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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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001956498.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 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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Familial melanoma: clinical factors associated with germline CDKN2A mutations according to the number of patients affected by melanoma in a family. | Maubec E | Journal of the American Academy of Dermatology | 2012 | PMID: 22841127 |
The contribution of large genomic deletions at the CDKN2A locus to the burden of familial melanoma. | Lesueur F | British journal of cancer | 2008 | PMID: 18612309 |
Population-based prevalence of CDKN2A and CDK4 mutations in patients with multiple primary melanomas. | Helsing P | Genes, chromosomes & cancer | 2008 | PMID: 18023021 |
A novel type of deletion in the CDKN2A gene identified in a melanoma-prone family. | Knappskog S | Genes, chromosomes & cancer | 2006 | PMID: 17001621 |
Text-mined citations for rs1063045 ...
HelpRecord last updated Oct 13, 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.