ClinVar Genomic variation as it relates to human health
NM_000059.4(BRCA2):c.700del (p.Ser234fs)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000059.4(BRCA2):c.700del (p.Ser234fs)
Variation ID: 38079 Accession: VCV000038079.23
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 13q13.1 13: 32330933 (GRCh38) [ NCBI UCSC ] 13: 32905070 (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 Apr 1, 2014 May 1, 2024 Sep 8, 2016 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000059.4:c.700del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000050.3:p.Ser234fs frameshift NM_000059.3:c.696delT frameshift NC_000013.11:g.32330937del NC_000013.10:g.32905074del NG_012772.3:g.20458del LRG_293:g.20458del LRG_293t1:c.700del U43746.1:n.928delT - Protein change
- Other names
- 924delT
- 928delT
- Canonical SPDI
- NC_000013.11:32330932:TTTTT:TTTT
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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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BRCA2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
18747 | 18905 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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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 (5) |
reviewed by expert panel
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Sep 8, 2016 | RCV000031661.19 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Oct 13, 2023 | RCV000045101.21 | |
Pathogenic (2) |
criteria provided, single submitter
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Dec 3, 2019 | RCV000486024.12 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Mar 31, 2022 | RCV000509624.16 | |
Pathogenic (1) |
no assertion criteria provided
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Jan 15, 2016 | RCV000735597.9 |
Submissions - Germline
Classification
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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
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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
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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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Pathogenic
(Sep 08, 2016)
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reviewed by expert panel
Method: curation
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Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
germline
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Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000300347.2
First in ClinVar: Sep 24, 2016 Last updated: Sep 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
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Pathogenic
(Oct 07, 2019)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast and ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000695027.2
First in ClinVar: Dec 26, 2017 Last updated: Jun 22, 2020 |
Comment:
Variant summary: BRCA2 c.700delT (p.Ser234ProfsX7) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: BRCA2 c.700delT (p.Ser234ProfsX7) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 250024 control chromosomes (gnomAD). c.700delT has been reported in the literature in several individuals affected with Hereditary Breast and Ovarian Cancer (e.g. Nedelcu_2002, Giannini_2006, Seong_2009, Kluska_2015). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Eight other submitters, including one expert panel (ENIGMA) have provided clinical-significance assessments for this variant in ClinVar after 2014, and all of them classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Dec 03, 2019)
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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: SCV000568443.5
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 in large population cohorts (Lek 2016); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Observed in individuals with BRCA2-related cancers (Nedelcu 2002, Lubinski 2004, Giannini 2006, Sinilnikova 2006, Seong 2009, Kim 2012, Germani 2018; Also known as 924delT and 928delT; This variant is associated with the following publications: (PMID: 15131399, 11938448, 16847550, 16528604, 26843898, 22798144, 19656164, 25948282, 22762150, 30263092, 31921681) (less)
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Pathogenic
(Mar 27, 2015)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 2
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000296691.2
First in ClinVar: Mar 17, 2015 Last updated: Jan 03, 2022 |
Indication for testing: Hereditary breast and ovarian cancer syndrome (HBOC)
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Pathogenic
(Oct 02, 2015)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
germline
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Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge
Accession: SCV000327578.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
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Pathogenic
(Nov 02, 2021)
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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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Color Diagnostics, LLC DBA Color Health
Accession: SCV000689026.4
First in ClinVar: Feb 19, 2018 Last updated: Feb 14, 2024 |
Comment:
This variant deletes 1 nucleotide in exon 9 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is expected to … (more)
This variant deletes 1 nucleotide in exon 9 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in at least six individuals affected with breast cancer and in additional suspected hereditary breast and ovarian cancer families (PMID: 11802209, 11938448, 16760289, 19656164, 22762150, 26843898). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less)
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Pathogenic
(Oct 13, 2023)
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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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Invitae
Accession: SCV000073114.10
First in ClinVar: Jul 03, 2013 Last updated: Feb 28, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Ser234Profs*7) in the BRCA2 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Ser234Profs*7) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with a personal and/or family history of breast and/or ovarian cancer (PMID: 11938448, 19656164, 22762150, 22798144, 26843898). This variant is also known as 924delT or 928delT. ClinVar contains an entry for this variant (Variation ID: 38079). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Mar 31, 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: SCV000608275.5
First in ClinVar: Oct 23, 2017 Last updated: May 01, 2024 |
Comment:
The c.700delT pathogenic mutation, located in coding exon 8 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 700, causing … (more)
The c.700delT pathogenic mutation, located in coding exon 8 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 700, causing a translational frameshift with a predicted alternate stop codon. This mutation has been previously identified in Italian, German, and Korean breast/ovarian cancer cohorts (Meindl A et al. Int. J. Cancer, 2002 Feb;97:472-80; Capalbo C et al. Ann. Oncol., 2006 Jun;17 Suppl 7:vii34-40; Seong MW et al. Clin. Genet., 2009 Aug;76:152-60). Of note, this alteration has also been designated as 928delT in the published literature. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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)
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Pathogenic
(Feb 20, 2004)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 2
Affected status: yes
Allele origin:
germline
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Breast Cancer Information Core (BIC) (BRCA2)
Accession: SCV000147525.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 2
Observation 2:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European
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Pathogenic
(Jan 15, 2016)
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no assertion criteria provided
Method: clinical testing
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Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
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Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000863735.1 First in ClinVar: Dec 24, 2018 Last updated: Dec 24, 2018 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000591708.2 First in ClinVar: Aug 27, 2017 Last updated: Apr 13, 2021 |
Comment:
The p.Ser234ProfsX7 deletion variant was identified in 4 of 6352 proband chromosomes (frequency: 0.001) from individuals or families with breast or ovarian cancer (Capalbo 2006, … (more)
The p.Ser234ProfsX7 deletion variant was identified in 4 of 6352 proband chromosomes (frequency: 0.001) from individuals or families with breast or ovarian cancer (Capalbo 2006, Kim 2012, Meindl 2002, Nedelcu 2002). The variant was also identified in dbSNP (ID: rs80359630) “With Pathogenic allele”, HGMD, ClinVar database, the BIC database (3X with clinical importance), and UMD (6X as a causal variant). The variant was classified as a pathogenic variant by the Sharing Clinical Reports Project (SCRP) (submitted within the ClinVar database and derived from Myriad reports). The p.Ser234ProfsX7 deletion variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 234 and leads to a premature stop codon 7 codons downstream. This alteration is then predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the BRCA2 gene are an established mechanism of disease in hereditary breast and ovarian cancer and is the type of variant expected to cause the disorder. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic. (less)
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Pathogenic
(Aug 16, 2011)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 2
Affected status: not provided
Allele origin:
germline
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Sharing Clinical Reports Project (SCRP)
Accession: SCV000054268.4
First in ClinVar: Apr 04, 2013 Last updated: Sep 27, 2014 |
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Pathogenic
(Jan 31, 2014)
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no assertion criteria provided
Method: research
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Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
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Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000587564.1 First in ClinVar: Aug 05, 2017 Last updated: Aug 05, 2017 |
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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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Recurrent mutations of BRCA1, BRCA2 and PALB2 in the population of breast and ovarian cancer patients in Southern Poland. | Wojcik P | Hereditary cancer in clinical practice | 2016 | PMID: 26843898 |
New recurrent BRCA1/2 mutations in Polish patients with familial breast/ovarian cancer detected by next generation sequencing. | Kluska A | BMC medical genomics | 2015 | PMID: 25948282 |
Novel and recurrent BRCA2 mutations in Italian breast/ovarian cancer families widen the ovarian cancer cluster region boundaries to exons 13 and 14. | Coppa A | Breast cancer research and treatment | 2014 | PMID: 25395318 |
Characteristics and spectrum of BRCA1 and BRCA2 mutations in 3,922 Korean patients with breast and ovarian cancer. | Kim H | Breast cancer research and treatment | 2012 | PMID: 22798144 |
Variation in breast cancer risk associated with factors related to pregnancies according to truncating mutation location, in the French National BRCA1 and BRCA2 mutations carrier cohort (GENEPSO). | Lecarpentier J | Breast cancer research : BCR | 2012 | PMID: 22762150 |
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 |
Comprehensive mutational analysis of BRCA1/BRCA2 for Korean breast cancer patients: evidence of a founder mutation. | Seong MW | Clinical genetics | 2009 | PMID: 19656164 |
Novel BRCA1 and BRCA2 germline mutations and assessment of mutation spectrum and prevalence in Italian breast and/or ovarian cancer families. | Giannini G | Breast cancer research and treatment | 2006 | PMID: 16847550 |
BRCA1 and BRCA2 genetic testing in Italian breast and/or ovarian cancer families: mutation spectrum and prevalence and analysis of mutation prediction models. | Capalbo C | Annals of oncology : official journal of the European Society for Medical Oncology | 2006 | PMID: 16760289 |
BRCA mutations in Italian breast/ovarian cancer families. | Nedelcu R | European journal of human genetics : EJHG | 2002 | PMID: 11938448 |
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 |
The breast cancer information core: database design, structure, and scope. | Szabo C | Human mutation | 2000 | PMID: 10923033 |
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Text-mined citations for rs80359630 ...
HelpRecord last updated Jun 17, 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.