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NM_000059.4(BRCA2):c.5238dup (p.Asn1747Ter)

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Interpretation:
Pathogenic​

Review status:
reviewed by expert panel
Submissions:
26 (Most recent: Sep 24, 2021)
Last evaluated:
Sep 8, 2016
Accession:
VCV000037954.24
Variation ID:
37954
Description:
1bp duplication
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NM_000059.4(BRCA2):c.5238dup (p.Asn1747Ter)

Allele ID
46510
Variant type
Duplication
Variant length
1 bp
Cytogenetic location
13q13.1
Genomic location
13: 32339592-32339593 (GRCh38) GRCh38 UCSC
13: 32913730 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NM_000059.4:c.5238dupT MANE Select
NM_000059.3:c.5238dupT nonsense
U43746.1:n.5466_5467insT
... more HGVS
Protein change
N1747*
Other names
5466insT
Canonical SPDI
NC_000013.11:32339592:T:TT
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
Breast Cancer Information Core (BIC) (BRCA2): 5466&base_change=ins T
ClinGen: CA021826
dbSNP: rs80359499
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 6 reviewed by expert panel Sep 8, 2016 RCV000031535.10
Pathogenic 3 criteria provided, multiple submitters, no conflicts Sep 29, 2020 RCV000130726.8
Pathogenic 7 criteria provided, multiple submitters, no conflicts Jun 17, 2021 RCV000212240.12
Pathogenic 5 criteria provided, multiple submitters, no conflicts Oct 18, 2020 RCV000257922.11
Pathogenic 2 criteria provided, single submitter Sep 28, 2018 RCV001170969.2
Pathogenic 1 criteria provided, single submitter Jan 1, 2019 RCV001262734.1
Pathogenic 1 criteria provided, single submitter Dec 1, 2013 RCV001642364.1
Pathogenic 1 no assertion criteria provided - RCV001353486.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
BRCA2 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
14116 14229

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Sep 08, 2016)
reviewed by expert panel
Method: curation
Breast-ovarian cancer, familial 2
Allele origin: germline
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000300851.2
Submitted: (Sep 13, 2016)
Evidence details
Comment:
Variant allele predicted to encode a truncated non-functional protein.
Pathogenic
(Dec 21, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000185615.6
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (6)
Comment:
The c.5238dupT pathogenic mutation (also known as p.N1747*), located in coding exon 10 of the BRCA2 gene, results from a duplication of T at nucleotide … (more)
Pathogenic
(Sep 29, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000905014.3
Submitted: (Jun 11, 2021)
Evidence details
Comment:
This variant inserts 1 nucleotide in exon 11 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is expected to … (more)
Pathogenic
(Apr 21, 2016)
criteria provided, single submitter
Method: clinical testing
Breast-ovarian cancer, familial 2
Allele origin: germline
Michigan Medical Genetics Laboratories,University of Michigan
Accession: SCV000267778.1
Submitted: (Apr 21, 2016)
Evidence details
Pathogenic
(Dec 28, 2015)
criteria provided, single submitter
Method: clinical testing
Breast-ovarian cancer, familial 2
Allele origin: unknown
Counsyl
Accession: SCV000488096.1
Submitted: (Nov 23, 2016)
Evidence details
Publications
PubMed (5)
Pathogenic
(Apr 20, 2017)
criteria provided, single submitter
Method: clinical testing
Hereditary breast and ovarian cancer syndrome
Allele origin: germline
Department of Pathology and Molecular Medicine,Queen's University
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000588099.1
Submitted: (Aug 04, 2017)
Evidence details
Pathogenic
(Feb 27, 2016)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000296566.2
Submitted: (Aug 01, 2017)
Evidence details
Publications
PubMed (4)
Pathogenic
(Oct 18, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary breast and ovarian cancer syndrome
Allele origin: germline
Invitae
Accession: SCV000072631.9
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (7)
Comment:
This sequence change creates a premature translational stop signal (p.Asn1747*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein … (more)
Pathogenic
(Dec 07, 2020)
criteria provided, single submitter
Method: clinical testing
Not provided
Allele origin: germline
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV001716155.1
Submitted: (May 26, 2021)
Evidence details
Publications
PubMed (6)
Comment:
PVS1, PM2, PP5
Pathogenic
(Dec 01, 2013)
criteria provided, single submitter
Method: curation
Breast-ovarian cancer, familial 1
Breast-ovarian cancer, familial 2
Hereditary breast and ovarian cancer syndrome
Allele origin: germline
Research and Development, ARUP Laboratories
Accession: SCV001854062.1
Submitted: (Sep 09, 2021)
Evidence details
Publications
PubMed (1)
Other databases
https://arup.utah.edu/database/B…
Pathogenic
(Oct 02, 2015)
criteria provided, single submitter
Method: clinical testing
Breast-ovarian cancer, familial 2
Allele origin: germline
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge
Accession: SCV000327184.3
Submitted: (Oct 28, 2016)
Evidence details
Pathogenic
(Nov 06, 2015)
criteria provided, single submitter
Method: clinical testing
Hereditary breast and ovarian cancer syndrome
Allele origin: germline
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000219349.3
Submitted: (Aug 28, 2017)
Evidence details
Pathogenic
(Feb 13, 2017)
criteria provided, single submitter
Method: clinical testing
Hereditary breast and ovarian cancer syndrome
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000694848.1
Submitted: (Jan 25, 2018)
Evidence details
Publications
PubMed (6)
Comment:
Variant summary: The BRCA2 c.5238dupT (p.Asn174X) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein due to nonsense … (more)
Pathogenic
(Jan 16, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.
Accession: SCV000747811.1
Submitted: (Jan 23, 2018)
Evidence details
Pathogenic
(Sep 28, 2018)
criteria provided, single submitter
Method: clinical testing
Breast and/or ovarian cancer
Allele origin: germline
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario
Accession: SCV001333629.1
Submitted: (Mar 03, 2020)
Evidence details
Pathogenic
(Jan 01, 2019)
criteria provided, single submitter
Method: clinical testing
Familial cancer of breast
Allele origin: unknown
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001440711.1
Submitted: (Oct 12, 2020)
Evidence details
Pathogenic
(Sep 22, 2017)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Clinical Genetics Karolinska University Hospital,Karolinska University Hospital
Accession: SCV001449908.1
Submitted: (Nov 26, 2020)
Evidence details
Pathogenic
(Jun 17, 2021)
criteria provided, single submitter
Method: clinical testing
not provided
(Autosomal dominant inheritance)
Allele origin: germline
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001762063.1
Submitted: (Jun 17, 2021)
Evidence details
Pathogenic
(Jan 26, 2021)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000210763.9
Submitted: (Sep 24, 2021)
Evidence details
Comment:
Nonsense 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; Reported … (more)
Pathogenic
(May 06, 2011)
no assertion criteria provided
Method: clinical testing
Breast-ovarian cancer, familial 2
Allele origin: germline
Sharing Clinical Reports Project (SCRP)
Accession: SCV000054140.4
Submitted: (Aug 20, 2015)
Evidence details
Pathogenic
(Jan 31, 2014)
no assertion criteria provided
Method: research
Hereditary breast and ovarian cancer syndrome
Allele origin: germline
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000587753.1
Submitted: (Aug 04, 2017)
Evidence details
Pathogenic
(Jun 11, 2019)
no assertion criteria provided
Method: clinical testing
Breast and/or ovarian cancer
Allele origin: germline
CZECANCA consortium
Accession: SCV001451857.1
Submitted: (Jun 13, 2019)
Evidence details
Publications
PubMed (1)
Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
Malignant tumor of breast
Allele origin: unknown
Department of Pathology and Laboratory Medicine,Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000591954.2
Submitted: (Mar 31, 2021)
Evidence details
Comment:
The BRCA2 p.Asn1747X variant was identified in 3 of 1936 proband chromosomes (frequency: 0.002) from German and Czech individuals or families with breast/ovarian or triple … (more)
Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001741278.3
Submitted: (Sep 02, 2021)
Evidence details
Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
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: SCV001972057.1
Submitted: (Sep 21, 2021)
Evidence details
not provided
(-)
no assertion provided
Method: clinical testing
Breast-ovarian cancer, familial 2
Allele origin: germline, somatic
Breast Cancer Information Core (BIC) (BRCA2)
Accession: SCV000146580.1
Submitted: (Mar 28, 2014)
Evidence details

Functional evidence

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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 this variant

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Title Author Journal Year Link
Multigene Panel Germline Testing of 1333 Czech Patients with Ovarian Cancer. Lhotova K Cancers 2020 PMID: 32295079
Dealing With BRCA1/2 Unclassified Variants in a Cancer Genetics Clinic: Does Cosegregation Analysis Help? Zuntini R Frontiers in genetics 2018 PMID: 30254663
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Analysis of protein-coding genetic variation in 60,706 humans. Lek M Nature 2016 PMID: 27535533
Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing. Susswein LR Genetics in medicine : official journal of the American College of Medical Genetics 2016 PMID: 26681312
Development and Validation of a Next-Generation Sequencing Assay for BRCA1 and BRCA2 Variants for the Clinical Laboratory. Strom CM PloS one 2015 PMID: 26295337
HBOC multi-gene panel testing: comparison of two sequencing centers. Schroeder C Breast cancer research and treatment 2015 PMID: 26022348
Prevalence of BRCA1 and BRCA2 germline mutations in patients with triple-negative breast cancer. Wong-Brown MW Breast cancer research and treatment 2015 PMID: 25682074
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
The contribution of deleterious germline mutations in BRCA1, BRCA2 and the mismatch repair genes to ovarian cancer in the population. Song H Human molecular genetics 2014 PMID: 24728189
Clinical characteristics of ovarian cancer classified by BRCA1, BRCA2, and RAD51C status. Cunningham JM Scientific reports 2014 PMID: 24504028
Mutation analysis of BRCA1, BRCA2, PALB2 and BRD7 in a hospital-based series of German patients with triple-negative breast cancer. Pern F PloS one 2012 PMID: 23110154
Breast and ovarian cancer risk and risk reduction in Jewish BRCA1/2 mutation carriers. Finkelman BS Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2012 PMID: 22430266
Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study. Borg A Human mutation 2010 PMID: 20104584
The relative contribution of point mutations and genomic rearrangements in BRCA1 and BRCA2 in high-risk breast cancer families. Palma MD Cancer research 2008 PMID: 18703817
Genetic testing in an ethnically diverse cohort of high-risk women: a comparative analysis of BRCA1 and BRCA2 mutations in American families of European and African ancestry. Nanda R JAMA 2005 PMID: 16234499
High proportion of recurrent germline mutations in the BRCA1 gene in breast and ovarian cancer patients from the Prague area. Pohlreich P Breast cancer research : BCR 2005 PMID: 16168118
Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population. Meindl A International journal of cancer 2002 PMID: 11802209
Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk. Frank TS Journal of clinical oncology : official journal of the American Society of Clinical Oncology 1998 PMID: 9667259
https://arup.utah.edu/database/BRCA/Variants/BRCA2.php - - - -

Text-mined citations for rs80359499...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 07, 2021