ClinVar Genomic variation as it relates to human health
NM_000059.4(BRCA2):c.1813dup (p.Ile605fs)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000059.4(BRCA2):c.1813dup (p.Ile605fs)
Variation ID: 37762 Accession: VCV000037762.107
- Type and length
-
Duplication, 1 bp
- Location
-
Cytogenetic: 13q13.1 13: 32333283-32333284 (GRCh38) [ NCBI UCSC ] 13: 32907428 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Oct 13, 2024 Apr 22, 2016 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000059.4:c.1813dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000050.3:p.Ile605fs frameshift NM_000059.3:c.1806dupA NM_000059.3:c.1813dupA NC_000013.11:g.32333291dup NC_000013.10:g.32907428dup NG_012772.3:g.22812dup LRG_293:g.22812dup U43746.1:n.2041_2042insA - Protein change
- I605fs
- Other names
- 2034insA
- 2041_2042insA
- p.Ile605AsnfsX11
- 2041insA
- 2040insA
- Canonical SPDI
- NC_000013.11:32333283:AAAAAAAA:AAAAAAAAA
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- loss_of_function_variant Sequence Ontology [SO:0002054]
-
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.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
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 | ||
---|---|---|---|---|---|---|
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. |
|||
BRCA2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
18955 | 19114 |
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. |
---|---|---|---|---|
Pathogenic (18) |
reviewed by expert panel
|
Apr 22, 2016 | RCV000031343.41 | |
Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
|
Jan 30, 2024 | RCV000043897.34 | |
Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Nov 22, 2023 | RCV000131453.22 | |
Pathogenic (15) |
criteria provided, multiple submitters, no conflicts
|
Mar 1, 2024 | RCV000160269.55 | |
Pathogenic (2) |
criteria provided, single submitter
|
Jun 23, 2023 | RCV000768624.14 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Apr 22, 2024 | RCV001310172.12 | |
Pathogenic (1) |
no assertion criteria provided
|
Mar 4, 2021 | RCV001391213.9 | |
Likely pathogenic (1) |
no assertion criteria provided
|
Sep 12, 2021 | RCV001642272.9 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Sep 18, 2024 | RCV001762061.14 | |
Pathogenic (2) |
no assertion criteria provided
|
Mar 23, 2024 | RCV001824580.10 | |
not provided (1) |
no classification provided
|
- | RCV003330405.2 | |
click to load more click to collapse |
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. |
|
---|---|---|---|---|---|
Pathogenic
(Apr 22, 2016)
|
reviewed by expert panel
Method: curation
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
germline
|
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000282363.1
First in ClinVar: Jun 24, 2016 Last updated: Jun 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
|
|
Pathogenic
(Dec 03, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
inherited
|
Genomic Research Center, Shahid Beheshti University of Medical Sciences
Accession: SCV000746277.1
First in ClinVar: Mar 27, 2017 Last updated: Mar 27, 2017 |
Age: 40-49 years
Sex: female
Geographic origin: Iran
|
|
Pathogenic
(May 08, 2014)
|
criteria provided, single submitter
Method: literature only
|
Breast-ovarian cancer, familial 2
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000220297.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022 |
|
|
Pathogenic
(Jul 26, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002019152.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
|
|
Pathogenic
(Jan 30, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000071910.16
First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Ile605Asnfs*11) 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.Ile605Asnfs*11) 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). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with breast, ovarian, and prostate cancer (PMID: 9150150, 21324516, 21952622, 22535016, 22729890). It has also been observed to segregate with disease in related individuals. This variant is also known as 1813insA, 2041insA, and 2034insA. ClinVar contains an entry for this variant (Variation ID: 37762). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
Pathogenic
(Mar 05, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004211858.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
|
|
Pathogenic
(May 25, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
germline
|
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
Accession: SCV000839914.1
First in ClinVar: Mar 27, 2017 Last updated: Mar 27, 2017 |
Comment:
The c.1813dup (p.Ile605Asnfs*11) variant in the BRCA2 gene has been detected in multiple patients with breast and/or ovarian cancer [referred as 2034insA and 2041insA in … (more)
The c.1813dup (p.Ile605Asnfs*11) variant in the BRCA2 gene has been detected in multiple patients with breast and/or ovarian cancer [referred as 2034insA and 2041insA in PMID 9150150, 21324516, 22535016] and prostate cancer [PMID 21952622].This variant has been reported in four individuals from the ExAC database (http://exac.broadinstitute.org/variant/22-29091226-TA-T). This one bp duplication in exon 10 results in a frameshift and the creation of a premature stop codon. This variant is expected to result in a loss of function of the protein. It is thus classified as pathogenic. (less)
|
|
Likely pathogenic
(Jan 26, 2018)
|
criteria provided, single submitter
Method: research
|
Hereditary cancer-predisposing syndrome
Affected status: yes
Allele origin:
germline
|
Academic Department of Medical Genetics, University of Cambridge
Accession: SCV000992210.1
First in ClinVar: Sep 09, 2019 Last updated: Sep 09, 2019
Comment:
Identified as part of research study of individuals with multiple primary tumours referred for genetic assessment
|
Comment:
Application of AMCG guidelines 2015. Used other ClinVar submission evidence where relevant. Loss of heterozygosity in tumours or immunohistochemistry abnormalities considered functional evidence of pathogenicity.
Clinical Features:
Non-Hodgkin lymphoma (present) , Breast carcinoma (present) , Endometrial carcinoma (present)
|
|
Pathogenic
(Oct 23, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
(Unknown mechanism)
Affected status: yes
Allele origin:
germline
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001447436.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Ovarian neoplasm (present)
Sex: female
|
|
Pathogenic
(Dec 21, 2021)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002533267.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Comment:
The BRCA2 c.1813dupA (p.I605NfsX11) variant has been reported in heterozygosity in numerous individuals with breast, ovarian, pancreatic, or prostate cancer (PMID: 21324516, 28324225, 28726808, 29446198, … (more)
The BRCA2 c.1813dupA (p.I605NfsX11) variant has been reported in heterozygosity in numerous individuals with breast, ovarian, pancreatic, or prostate cancer (PMID: 21324516, 28324225, 28726808, 29446198, 21952622). It is also known as 2041insA and 2034insA in the literature. This variant is a well-established pathogenic variant associated with hereditary breast and ovarian cancer (PMID: 29446198). The variant causes a frameshift at amino acid 605 that results in premature termination 11 amino acids downstream, which is predicted cause nonsense-mediated decay and loss of function. Loss of function variants in BRCA2 are known to be pathogenic (PMID: 29446198). It was observed in 3/232106 chromosomes across all populations in the large and broad cohorts of the Genome Aggregation Database (http://gnomad.broadinstitute.org, PMID: 32461654) and has been reported in ClinVar (Variation ID: 37762). Based on the current evidence available, this variant is interpreted as pathogenic. (less)
|
|
|
Pathogenic
(Oct 02, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
germline
|
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge
Accession: SCV000326619.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
|
|
Pathogenic
(May 25, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
Affected status: yes
Allele origin:
germline
|
Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002556737.2
First in ClinVar: Aug 08, 2022 Last updated: Dec 17, 2022 |
|
|
Pathogenic
(Jun 09, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000210718.11
First in ClinVar: Feb 24, 2015 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; Observed … (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; Observed in individuals with hereditary breast and ovarian cancer (Frank 1998, Foretova 2004, Tai 2007, Kote-Jarai 2011, Becker 2012, Blay 2013, Pritzlaff 2017, Ibrahim 2018); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; This variant is associated with the following publications: (PMID: 21952622, 22535016, 9150150, 15024741, 18489799, 28324225, 30715675, 21324516, 23683081, 20104584, 25685387, 26834852, 22729890, 27225637, 27167707, 28008555, 22382806, 28873162, 28503720, 28664449, 28651617, 25085752, 23199084, 29433453, 21232165, 15689453, 9667259, 9585613, 25072261, 18042939, 28831036, 28724667, 29909963, 30720863, 28843361, 30014164, 30702160, 30322717, 30309722, 30257646, 21548014, 15070707, 28726808, 31454914, 26689913, 32318955, 31447099, 29176636, 32581362) (less)
|
|
Pathogenic
(Sep 27, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
germline
|
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Accession: SCV004099179.1
First in ClinVar: Oct 28, 2023 Last updated: Oct 28, 2023 |
Comment:
PVS1, PM2, PS4
Secondary finding: yes
|
|
Pathogenic
(Jun 23, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
|
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Study: Canadian Open Genetics Repository
Accession: SCV000219309.7 First in ClinVar: Mar 29, 2015 Last updated: Feb 04, 2024 |
|
|
Pathogenic
(Nov 22, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000683453.5
First in ClinVar: Feb 19, 2018 Last updated: Feb 14, 2024 |
Comment:
This variant inserts 1 nucleotide in exon 10 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is also known … (more)
This variant inserts 1 nucleotide in exon 10 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is also known as 2034insA, 2040insA, 2041insA, 2041dupA, 2041_2042insA, c.1813insA and c.1806dupA in the literature. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in a breast cancer case-control meta-analysis in 20 cases and 1 unaffected control, which is estimated to have an odds ratio for pathogenicity of OR=17.689 (95%CI 2.374 to 131.809; p-value<0.001) (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA2_001802) and has also been reported in individuals affected with breast, ovarian, pancreatic, prostate and neuroendocrine cancers (PMID: 9150150, 9667259, 18042939, 20104584, 21324516, 21952622, 22729890, 25072261, 28724667, 29433453) and suspected hereditary breast and ovarian cancer families (PMID: 11802209, 21232165, 24156927). In one family, this variant was reported in 11 women affected with breast cancer across three generations (PMID: 9150150). This variant also has been detected in two compound heterozygous individuals with a second pathogenic BRCA2 mutation who exhibited clinical features consistent with Fanconi anemia (PMID: 15070707, 21548014). Haplotype analysis suggests that this variant may be a founder mutation and is common in people of German ancestry (PMID: 9585613, 23199084). This variant has been identified in 3/232106 chromosomes 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)
|
|
Pathogenic
(Mar 23, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV004562779.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
The BRCA2 c.1813dup; p.Ile605AsnfsTer11 variant (rs80359306), also known as 2041insA and 2034insA, is reported in the literature in several individuals with HBOC-related cancers (Becker 2012, … (more)
The BRCA2 c.1813dup; p.Ile605AsnfsTer11 variant (rs80359306), also known as 2041insA and 2034insA, is reported in the literature in several individuals with HBOC-related cancers (Becker 2012, Foretova 2004, Ibrahim 2018, Zhang 2011), and was demonstrated to segregate with disease in a large German family (Schubert 1997). This variant has also been reported in patients with prostate and other cancers (Ibrahim 2018, Kote-Jarai 2011). This variant is reported in ClinVar and is classified as pathogenic by an expert panel (Variation ID: 37762). This variant is only found on three alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. This variant causes a frameshift by inserting a single nucleotide, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Functional data indicate that cell lines derived from patients harboring the c.1813dup variant are more susceptible than wild-type to radiation induced chromosomal abnormalities (Becker 2012). Based on available information, the p.Ile605AsnfsTer11 variant is considered to be pathogenic. REFERENCES Becker et al. A 24-color metaphase-based radiation assay discriminates heterozygous BRCA2 mutation carriers from controls by chromosomal radiosensitivity. Breast Cancer Res Treat. 2012; 135(1): 167-175. PMID: 22729890. Foretova et al. BRCA1 and BRCA2 mutations in women with familial or early-onset breast/ovarian cancer in the Czech Republic. Hum Mutat. 2004 Apr; 23(4): 397-398. PMID: 15024741. Ibrahim M et al. Male BRCA mutation carriers: clinical characteristics and cancer spectrum. BMC Cancer. 2018 Feb 13;18(1):179. PMID: 29433453. Kote-Jarai et al. BRCA2 is a moderate penetrance gene contributing to young-onset prostate cancer: implications for genetic testing in prostate cancer patients. Br J Cancer. 2011; 105(8): 1230-1234. PMID: 21952622. Schubert et al. BRCA2 in American families with four or more cases of breast or ovarian cancer: recurrent and novel mutations, variable expression, penetrance, and the possibility of families whose cancer is not attributable to BRCA1 or BRCA2. Am J Hum Genet. 1997; 60(5): 1031-1040. PMID: 9150150. Zhang et al. Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer. Gynecol Oncol. 2011; 121(2): 353-357. PMID: 21324516. (less)
|
|
Pathogenic
(Feb 05, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004846973.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
|
Comment:
This variant inserts 1 nucleotide in exon 10 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is also known … (more)
This variant inserts 1 nucleotide in exon 10 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is also known as 2034insA, 2040insA, 2041insA, 2041dupA, 2041_2042insA, c.1813insA and c.1806dupA in the literature. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in a breast cancer case-control meta-analysis in 20 cases and 1 unaffected control, which is estimated to have an odds ratio for pathogenicity of OR=17.689 (95%CI 2.374 to 131.809; p-value<0.001) (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA2_001802) and also has been reported in individuals affected with breast, ovarian, pancreatic, prostate and neuroendocrine cancers (PMID: 9150150, 9667259, 18042939, 20104584, 21324516, 21952622, 22729890, 25072261, 28724667, 29433453) and suspected hereditary breast and ovarian cancer families (PMID: 11802209, 21232165, 24156927). In one family, this variant was reported in 11 women affected with breast cancer across three generations (PMID: 9150150). This variant also has been detected in two compound heterozygous individuals with a second pathogenic BRCA2 mutation who exhibited clinical features consistent with Fanconi anemia (PMID: 15070707, 21548014). Haplotype analysis suggests that this variant may be a founder mutation and is common in people of German ancestry (PMID: 9585613, 23199084). This variant has been identified in 3/232106 chromosomes 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)
Number of individuals with the variant: 2
|
|
Pathogenic
(May 27, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics Laboratory, Skane University Hospital Lund
Accession: SCV005199775.1
First in ClinVar: Aug 25, 2024 Last updated: Aug 25, 2024 |
|
|
Pathogenic
(Mar 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001247641.25
First in ClinVar: May 12, 2020 Last updated: Oct 08, 2024 |
Comment:
BRCA2: PVS1, PS4, PM2
Number of individuals with the variant: 16
|
|
Pathogenic
(Apr 22, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
unknown
|
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV003804730.2
First in ClinVar: Mar 04, 2023 Last updated: Oct 13, 2024 |
Comment:
Criteria applied: PVS1,PS4,PM5_STR
Clinical Features:
Breast carcinoma (present)
Sex: female
|
|
Pathogenic
(Oct 27, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
unknown
|
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001428710.4
First in ClinVar: Aug 17, 2020 Last updated: Oct 13, 2024 |
Comment:
Criteria applied: PVS1,PM5_STR
Clinical Features:
Family history of cancer (present)
Sex: female
|
|
Pathogenic
(Sep 18, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
unknown
|
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV004032245.2
First in ClinVar: Sep 09, 2023 Last updated: Oct 13, 2024 |
Comment:
Criteria applied: PVS1,PS4, PM5_PTC_S
Clinical Features:
Breast carcinoma (present)
Sex: female
|
|
Pathogenic
(Nov 03, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
germline
|
Michigan Medical Genetics Laboratories, University of Michigan
Accession: SCV000195964.1
First in ClinVar: Jan 01, 2016 Last updated: Jan 01, 2016 |
Tissue: Blood
|
|
Pathogenic
(Jan 01, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
germline
|
Genologica Medica
Additional submitter:
Servicio Andaluz de Salud, Hospital Universitario Virgen de la Victoria
Accession: SCV000577948.1
First in ClinVar: Mar 27, 2017 Last updated: Mar 27, 2017 |
Family history: yes
Ethnicity/Population group: Causasians
Geographic origin: Spain
Tissue: Blood
Secondary finding: no
|
|
Pathogenic
(Oct 20, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast and ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000918819.1
First in ClinVar: Jun 03, 2019 Last updated: Jun 03, 2019 |
Comment:
Variant summary: The BRCA2 c.1813dupA (p.Ile605AsnfsX11) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein due to nonsense … (more)
Variant summary: The BRCA2 c.1813dupA (p.Ile605AsnfsX11) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.1842dupT/ p.Asn615X, c.1889delC/ p.Thr630fsX14, etc). One in silico tool predicts a damaging outcome for this variant. This variant was found in 8/227550 control chromosomes at a frequency of 0.0000352, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). This variant has been reported in numerous affected individuals/families and has been classified this variant as pathogenic by multiple clinical diagnostic laboratories/reputable databases. Functional study showed variant with diminished DNA double strand break repair capacity (Becker_2012). Taken together, this variant is classified as pathogenic. (less)
|
|
Pathogenic
(Feb 08, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
(Autosomal dominant inheritance)
Affected status: not provided
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000605784.2
First in ClinVar: Aug 27, 2017 Last updated: Dec 26, 2017 |
Comment:
The p.Ile605fs variant in BRCA2 has been reported in >75 individuals with BRCA2- associated cancers (Breast Cancer Information Core (BIC) database), and segregat ed with … (more)
The p.Ile605fs variant in BRCA2 has been reported in >75 individuals with BRCA2- associated cancers (Breast Cancer Information Core (BIC) database), and segregat ed with disease in 7 affected relatives from 1 family (Schubert 1997). This vari ant has also been identified in 3/63362 European chromosomes by the Exome Aggreg ation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs80359306); howev er, this frequency is low enough to be consistent with the frequency of heredita ry breast and ovarian cancer (HBOC) in the general population. The p.Ile605fs va riant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 605 and leads to a premature termination codon 11 amino acids downstream. This alteration is then predicted to lead to a truncate d or absent protein. Heterozygous loss of function of the BRCA2 gene is an estab lished disease mechanism for HBOC. In summary, this variant meets our criteria t o be classified as pathogenic for HBOC in an autosomal dominant manner based upo n segregation studies, absence from controls, and predicted impact to protein. (less)
Number of individuals with the variant: 3
|
|
Pathogenic
(Jan 01, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast and ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
GeneKor MSA
Accession: SCV000693558.2
First in ClinVar: Dec 26, 2017 Last updated: May 04, 2020 |
Comment:
This sequence change inserts one nucleotide in exon 10 of the BRCA2 mRNA (c.1813dupA), causing a frameshift after codon 605. This creates a premature translational … (more)
This sequence change inserts one nucleotide in exon 10 of the BRCA2 mRNA (c.1813dupA), causing a frameshift after codon 605. This creates a premature translational stop signal 11 amino acid residues later (p.Ile605Asnfs*11) and is expected to result in an absent or disrupted protein product. Truncating variants in BRCA2 are known to be pathogenic. This particular variant has been reported in individuals affected with breast, ovarian, and prostate cancer (PMID: 9150150, 21952622, 22535016). The mutation database ClinVar contains entries for this variant (Variation ID: 37762). (less)
|
|
Pathogenic
(Nov 23, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics and Genomics, Karolinska University Hospital
Accession: SCV001450011.1
First in ClinVar: Dec 12, 2020 Last updated: Dec 12, 2020 |
Number of individuals with the variant: 6
|
|
Pathogenic
(Apr 02, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Department of Molecular Diagnostics, Institute of Oncology Ljubljana
Accession: SCV001499767.1
First in ClinVar: Mar 07, 2021 Last updated: Mar 07, 2021 |
|
|
Pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
University of Science and Technology Houari Boumediene, Laboratory of Molecular and Cellular Biology (LBCM)
Accession: SCV002104297.2
First in ClinVar: Mar 28, 2022 Last updated: Mar 28, 2022 |
Age: 30-39 years
Sex: female
Geographic origin: Algeria
|
|
Pathogenic
(May 02, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
germline
|
MGZ Medical Genetics Center
Accession: SCV002579911.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PVS1, PP1_STR, PS4_MOD, PM2_SUP, PM3_SUP
|
Number of individuals with the variant: 7
Sex: male
|
|
Pathogenic
(Jul 02, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast and ovarian cancer syndrome
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV000838762.2
First in ClinVar: Oct 10, 2018 Last updated: Dec 11, 2022 |
|
|
Pathogenic
(Aug 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002761148.3
First in ClinVar: Dec 17, 2022 Last updated: Aug 18, 2023 |
|
|
Pathogenic
(Sep 20, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
(Unknown mechanism)
Affected status: yes
Allele origin:
germline
|
Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg
Accession: SCV004035905.1
First in ClinVar: Sep 23, 2023 Last updated: Sep 23, 2023 |
Comment:
This variant has been identified by standard clinical testing. Breast-ovarian cancer, familial, susceptibility to, 2
Number of individuals with the variant: 1
|
|
Pathogenic
(May 18, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000296732.7
First in ClinVar: Jun 24, 2016 Last updated: Jan 06, 2024 |
Comment:
The BRCA2 c.1813dup (p.Ile605Asnfs*11) variant alters the translational reading frame of the BRCA2 mRNA and causes the premature termination of BRCA2 protein synthesis. This variant … (more)
The BRCA2 c.1813dup (p.Ile605Asnfs*11) variant alters the translational reading frame of the BRCA2 mRNA and causes the premature termination of BRCA2 protein synthesis. This variant has been reported in the published literature in affected individuals with breast and/or ovarian cancer (PMIDs: 9150150 (1997), 21324516 (2011), 22729890 (2012), 28324225 (2017), 30257646 (2018), and 36169650 (2022)). In a large scale breast cancer association study, it was found in individuals with breast cancer as well as a control (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/BRCA2)). It has also been reported in individuals with prostate cancer (PMIDs: 29433453 (2018) and 32606146 (2020)). Based on the available information, this variant is classified as pathogenic. (less)
|
|
Pathogenic
(Jul 19, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not provided
Affected status: unknown
Allele origin:
germline
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV004225753.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
PP5, PM2, PS4_moderate, PVS1
Number of individuals with the variant: 3
|
|
Pathogenic
(Aug 25, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000186437.8
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
The c.1813dupA pathogenic mutation, located in coding exon 9 of the BRCA2 gene, results from a duplication of A at nucleotide position 1813, causing a … (more)
The c.1813dupA pathogenic mutation, located in coding exon 9 of the BRCA2 gene, results from a duplication of A at nucleotide position 1813, causing a translational frameshift with a predicted alternate stop codon (p.I605Nfs*11). This mutation has been detected in multiple individuals with breast, ovarian and prostate cancer from HBOC kindreds (Foretova L et al. Hum. Mutat. 2004 Apr;23:397-8; Janaviius R. EPMA J. 2010 Sept;1:397-412; Zhang S et al. Gynecol. Oncol. 2011 May;121:353-7; Kote-Jarai Z et al. Br. J. Cancer. 2011 Oct;105:1230-4; Carter NJ et al. Gynecol Oncol, 2018 12;151:481-488; Ibrahim M et al. BMC Cancer. 2018 02;18:179; Deng M et al. Int J Cancer, 2019 09;145:1517-1528; Mehemmai C et al. Pathol Oncol Res, 2020 Apr;26:715-726). In one study, this variant was reported in 20/60,466 breast cancer cases and in 1/53,461 controls (Dorling et al. N Engl J Med. 2021 02;384:428-439). This alteration, in compound heterozygosity with another BRCA2 mutation, was also reported in an individual with Fanconi anemia (Myers K et al. Pediatr. Blood Cancer. 2012 Mar;58:462-5). The c.1813dupA pathogenic mutation was reported in two unrelated probands with a personal and/or family history of breast/ovarian cancers and was shown to diminish DNA double strand break repair capacity in response to irradiation (Becker AA et al. Breast Cancer Res. Treat. 2012 Aug;135:167-75). Of note, this mutation is also referred to as 2041insA, 2034insA,and c.1806_1807insA in the published literature. 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)
|
|
Pathogenic
(Aug 05, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Department of Human Genetics, Hannover Medical School
Accession: SCV005093814.1
First in ClinVar: Aug 11, 2024 Last updated: Aug 11, 2024 |
Clinical Features:
Breast carcinoma (present)
|
|
Pathogenic
(Feb 11, 2015)
|
no assertion criteria provided
(clinical testing)
Method: clinical testing
|
Breast-ovarian cancer, familial 2
Affected status: yes
Allele origin:
germline
|
Institute of Human Genetics, Medical University Innsbruck
Study: BRCA-Tyrol
Accession: SCV000212013.1 First in ClinVar: Mar 03, 2015 Last updated: Mar 03, 2015
Comment:
BRCA-mutation spectrum Western Austria
|
|
|
Pathogenic
(Oct 11, 2013)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 2
Affected status: not provided
Allele origin:
germline
|
Sharing Clinical Reports Project (SCRP)
Accession: SCV000053947.5
First in ClinVar: Apr 04, 2013 Last updated: Jun 24, 2016 |
|
|
Pathogenic
(Jun 11, 2019)
|
no assertion criteria provided
Method: clinical testing
|
Breast and/or ovarian cancer
Affected status: yes
Allele origin:
germline
|
CZECANCA consortium
Accession: SCV001451796.1
First in ClinVar: Dec 26, 2020 Last updated: Dec 26, 2020 |
Number of individuals with the variant: 2
Ethnicity/Population group: Slavic
Geographic origin: Czech Republic
|
|
Pathogenic
(Mar 04, 2021)
|
no assertion criteria provided
Method: case-control
|
Carcinoma of pancreas
Affected status: yes
Allele origin:
germline
|
CZECANCA consortium
Accession: SCV001593129.1
First in ClinVar: May 16, 2021 Last updated: May 16, 2021 |
Number of individuals with the variant: 1
Ethnicity/Population group: Slavic
Geographic origin: Czech Republic
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001797345.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
|
|
Pathogenic
(May 24, 2021)
|
no assertion criteria provided
Method: case-control
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
germline
|
Molecular Oncology, Hospital Universitario Central de Asturias (HUCA)
Accession: SCV005061313.1
First in ClinVar: Oct 13, 2024 Last updated: Oct 13, 2024 |
Secondary finding: no
|
|
Pathogenic
(Mar 23, 2024)
|
no assertion criteria provided
Method: clinical testing
|
BRCA2-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000805657.2
First in ClinVar: Dec 19, 2017 Last updated: Oct 08, 2024 |
Comment:
The BRCA2 c.1813dupA variant is predicted to result in a frameshift and premature protein termination (p.Ile605Asnfs*11). This variant (alternatively described as 1813insA and 2041dupA) has … (more)
The BRCA2 c.1813dupA variant is predicted to result in a frameshift and premature protein termination (p.Ile605Asnfs*11). This variant (alternatively described as 1813insA and 2041dupA) has been documented multiple times in individuals with personal and/or family history of breast/ovarian cancers (Son et al. 2012. PubMed ID: 22382806; Meisel et al. 2017. PubMed ID: 28324225), and prostate cancer (Kote-Jarai et al. 2011. PubMed ID: 21952622). A functional in vitro study using blood lymphocytes on this variant has demonstrated significantly higher radiation-induced chromosomal aberrations (Becker et al. 2012. PubMed ID: 22729890). This variant is reported in 0.0066% of alleles in individuals of African descent in gnomAD and is classified as pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/37762/). Frameshift variants in BRCA2 are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
|
|
Pathogenic
(May 29, 2002)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 2
Affected status: yes
Allele origin:
germline,
somatic
|
Breast Cancer Information Core (BIC) (BRCA2)
Accession: SCV000145951.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 27
Observation 2:
Number of individuals with the variant: 1
Geographic origin: Austria
Observation 3:
Number of individuals with the variant: 2
Geographic origin: Western European
Observation 4:
Number of individuals with the variant: 1
Geographic origin: Western, Central/Eastern European
Observation 5:
Number of individuals with the variant: 1
Ethnicity/Population group: Ashkenazi, Western European
Observation 6:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: Czech Republic
Observation 7:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: Germany
Observation 8:
Number of individuals with the variant: 2
Ethnicity/Population group: Caucasian Non Hispanic
Observation 9:
Number of individuals with the variant: 2
Ethnicity/Population group: Central/Eastern European
Observation 10:
Number of individuals with the variant: 2
Ethnicity/Population group: Latin American, Caribbean
Observation 11:
Number of individuals with the variant: 2
Ethnicity/Population group: Native American
Observation 12:
Number of individuals with the variant: 1
Ethnicity/Population group: Near Eastern
Observation 13:
Number of individuals with the variant: 29
Ethnicity/Population group: Western European
Observation 14:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Central/Eastern European
Observation 15:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, German, Cyech
Observation 16:
Number of individuals with the variant: 1
Ethnicity/Population group: Western Europeanan, Central/Eastern European
Observation 17:
Number of individuals with the variant: 1
Ethnicity/Population group: Western, Central/Eastern European
Observation 18:
Number of individuals with the variant: 1
|
|
Pathogenic
(Jan 31, 2014)
|
no assertion criteria provided
Method: research
|
Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000587614.1 First in ClinVar: Aug 05, 2017 Last updated: Aug 05, 2017 |
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
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: SCV000591772.2 First in ClinVar: Aug 27, 2017 Last updated: Apr 13, 2021 |
Comment:
The BRCA2 p.Ile605AsnfsX11 variant was identified in 8 of 22770 proband chromosomes (frequency: 0.00035) from individuals or families with Breast, Ovarian, or Prostate cancer (Becker, … (more)
The BRCA2 p.Ile605AsnfsX11 variant was identified in 8 of 22770 proband chromosomes (frequency: 0.00035) from individuals or families with Breast, Ovarian, or Prostate cancer (Becker, 2012; Heidemann, 2012; Janavicius, 2010; Kote-Jarai, 2011; Schubert, 1997; Zhang, 2011). The variant was shown to segregate in at least nine affected individuals with breast cancer (Schubert, 1997; Heidemann, 2012). The variant was also identified in dbSNP (ID: rs80359306) “With pathogenic allele”, HGMD, the BIC database (75X with class 5 clinical importance), and UMD (18X as a causal variant). The c.1813dupA duplication variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 605 and leads to a premature stop codon 11 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)
Number of individuals with the variant: 4
|
|
Likely pathogenic
(Sep 12, 2021)
|
no assertion criteria provided
Method: clinical testing
|
Breast carcinoma
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Medical Genetics Laboratory, Umraniye Training and Research Hospital, University of Health Sciences
Accession: SCV001852758.1
First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021 |
Sex: female
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001905821.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
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: SCV001968680.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
|
|
Pathogenic
(Aug 26, 2022)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
germline
|
BRCAlab, Lund University
Accession: SCV002588853.1
First in ClinVar: Apr 01, 2023 Last updated: Apr 01, 2023 |
|
|
not provided
(-)
|
no classification provided
Method: phenotyping only
|
BRCA2-related disorder
Affected status: unknown
Allele origin:
unknown
|
GenomeConnect, ClinGen
Accession: SCV002075083.1
First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022 |
Comment:
Variant interpreted as Pathogenic and reported on 09-10-2018 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided … (more)
Variant interpreted as Pathogenic and reported on 09-10-2018 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. (less)
Clinical Features:
Melanoma (present) , Abnormality of vision (present) , Abnormal retinal morphology (present) , Tinnitus (present) , Hyperacusis (present) , Vertigo (present) , Cognitive impairment (present) … (more)
Melanoma (present) , Abnormality of vision (present) , Abnormal retinal morphology (present) , Tinnitus (present) , Hyperacusis (present) , Vertigo (present) , Cognitive impairment (present) , Abnormality of coordination (present) , Hypertonia (present) , Memory impairment (present) , Anxiety (present) , Depression (present) , Atrophic scars (present) , Cutaneous photosensitivity (present) , Joint hypermobility (present) , Abnormal muscle physiology (present) , Abnormality of the musculature of the limbs (present) , Cardiac arrhythmia (present) , Abnormality of the cardiovascular system (present) , Abnormal pattern of respiration (present) , Abnormal esophagus morphology (present) , Abnormal intestine morphology (present) , Gingivitis (present) (less)
Indication for testing: Diagnostic
Age: 30-39 years
Sex: female
Method: Sanger Sequencing
Testing laboratory: GeneDx
Date variant was reported to submitter: 2018-09-10
Testing laboratory interpretation: Pathogenic
|
|
not provided
(-)
|
no classification provided
Method: phenotyping only
|
Hereditary breast ovarian cancer syndrome
Fanconi anemia complementation group D1
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
unknown
|
GenomeConnect - Invitae Patient Insights Network
Accession: SCV004037528.1
First in ClinVar: Oct 07, 2023 Last updated: Oct 07, 2023 |
Comment:
Variant classified as Pathogenic and reported on 05-11-2017 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report … (more)
Variant classified as Pathogenic and reported on 05-11-2017 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. (less)
Clinical Features:
Abnormal muscle physiology (present) , Abnormality of the somatic nervous system (present)
Indication for testing: Diagnostic|Family Testing|Diagnostic test for a personal and family history of disease. Family variant testing
Age: 60-69 years
Sex: male
Method: Familial/Targeted Variant Analysis
Testing laboratory: Invitae
Date variant was reported to submitter: 2017-05-11
Testing laboratory interpretation: Pathogenic
|
|
click to load more click to collapse |
Germline Functional Evidence
Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for 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 functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
---|---|---|---|---|
loss_of_function_variant
|
University of Science and Technology Houari Boumediene, Laboratory of Molecular and Cellular Biology (LBCM)
Accession: SCV002104297.2
|
|
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Featuring BRCA1 and BRCA2 germline mutational landscape from Asturias (North Spain). | Pitiot AS | Clinical genetics | 2024 | PMID: 38922859 |
High detection rate from genetic testing in BRCA-negative women with familial epithelial ovarian cancer. | Flaum N | Genetics in medicine : official journal of the American College of Medical Genetics | 2022 | PMID: 36169650 |
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 |
Population genetic screening efficiently identifies carriers of autosomal dominant diseases. | Grzymski JJ | Nature medicine | 2020 | PMID: 32719484 |
Germline Mutations in DNA Repair Genes in Patients With Metastatic Castration-resistant Prostate Cancer. | Holeckova K | In vivo (Athens, Greece) | 2020 | PMID: 32606146 |
BRCA1 and BRCA2 Germline Mutation Analysis in Hereditary Breast/Ovarian Cancer Families from the Aures Region (Eastern Algeria): First Report. | Mehemmai C | Pathology oncology research : POR | 2020 | PMID: 30715675 |
Prevalence and clinical outcomes of germline mutations in BRCA1/2 and PALB2 genes in 2769 unselected breast cancer patients in China. | Deng M | International journal of cancer | 2019 | PMID: 30720863 |
Germline variation in BRCA1/2 is highly ethnic-specific: Evidence from over 30,000 Chinese hereditary breast and ovarian cancer patients. | Bhaskaran SP | International journal of cancer | 2019 | PMID: 30702160 |
Germline pathogenic variants identified in women with ovarian tumors. | Carter NJ | Gynecologic oncology | 2018 | PMID: 30322717 |
Addition of triple negativity of breast cancer as an indicator for germline mutations in predisposing genes increases sensitivity of clinical selection criteria. | Hoyer J | BMC cancer | 2018 | PMID: 30257646 |
Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. | Rebbeck TR | Human mutation | 2018 | PMID: 29446198 |
Male BRCA mutation carriers: clinical characteristics and cancer spectrum. | Ibrahim M | BMC cancer | 2018 | PMID: 29433453 |
Prevalence of germ-line mutations in cancer genes among pancreatic cancer patients with a positive family history. | Chaffee KG | Genetics in medicine : official journal of the American College of Medical Genetics | 2018 | PMID: 28726808 |
Germline Mutations in Cancer Susceptibility Genes in a Large Series of Unselected Breast Cancer Patients. | Sun J | Clinical cancer research : an official journal of the American Association for Cancer Research | 2017 | PMID: 28724667 |
Spectrum of genetic variants of BRCA1 and BRCA2 in a German single center study. | Meisel C | Archives of gynecology and obstetrics | 2017 | PMID: 28324225 |
Fanconi anemia-D1 due to homozygosity for the BRCA2 gene Cypriot founder mutation: A case report. | Loizidou MA | Oncology letters | 2016 | PMID: 26834852 |
Development and validation of a new algorithm for the reclassification of genetic variants identified in the BRCA1 and BRCA2 genes. | Pruss D | Breast cancer research and treatment | 2014 | PMID: 25085752 |
Overall survival and clinical characteristics of pancreatic cancer in BRCA mutation carriers. | Golan T | British journal of cancer | 2014 | PMID: 25072261 |
Central European BRCA2 mutation carriers: birth cohort status correlates with onset of breast cancer. | Tea MK | Maturitas | 2014 | PMID: 24156927 |
Mutational analysis of BRCA1 and BRCA2 in hereditary breast and ovarian cancer families from Asturias (Northern Spain). | Blay P | BMC cancer | 2013 | PMID: 23683081 |
A 24-color metaphase-based radiation assay discriminates heterozygous BRCA2 mutation carriers from controls by chromosomal radiosensitivity. | Becker AA | Breast cancer research and treatment | 2012 | PMID: 22729890 |
Double heterozygosity for mutations in BRCA1 and BRCA2 in German breast cancer patients: implications on test strategies and clinical management. | Heidemann S | Breast cancer research and treatment | 2012 | PMID: 22535016 |
The clinical phenotype of children with Fanconi anemia caused by biallelic FANCD1/BRCA2 mutations. | Myers K | Pediatric blood & cancer | 2012 | PMID: 21548014 |
BRCA2 is a moderate penetrance gene contributing to young-onset prostate cancer: implications for genetic testing in prostate cancer patients. | Kote-Jarai Z | British journal of cancer | 2011 | PMID: 21952622 |
Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer. | Zhang S | Gynecologic oncology | 2011 | PMID: 21324516 |
The occurrence of germline BRCA1 and BRCA2 sequence alterations in Slovenian population. | Stegel V | BMC medical genetics | 2011 | PMID: 21232165 |
Founder BRCA1/2 mutations in the Europe: implications for hereditary breast-ovarian cancer prevention and control. | Janavičius R | The EPMA journal | 2010 | PMID: 23199084 |
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 |
Spectrum and characterisation of BRCA1 and BRCA2 deleterious mutations in high-risk Czech patients with breast and/or ovarian cancer. | Machackova E | BMC cancer | 2008 | PMID: 18489799 |
Breast cancer risk among male BRCA1 and BRCA2 mutation carriers. | Tai YC | Journal of the National Cancer Institute | 2007 | PMID: 18042939 |
Biallelic BRCA2 mutations are associated with multiple malignancies in childhood including familial Wilms tumour. | Reid S | Journal of medical genetics | 2005 | PMID: 15689453 |
Germline mutations in BRCA2: shared genetic susceptibility to breast cancer, early onset leukemia, and Fanconi anemia. | Wagner JE | Blood | 2004 | PMID: 15070707 |
BRCA1 and BRCA2 mutations in women with familial or early-onset breast/ovarian cancer in the Czech Republic. | Foretova L | Human mutation | 2004 | PMID: 15024741 |
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 |
Detection of BRCA1 and BRCA2 mutations in breast cancer families by a comprehensive two-stage screening procedure. | Spitzer E | International journal of cancer | 2000 | PMID: 10699917 |
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 |
Haplotype and phenotype analysis of nine recurrent BRCA2 mutations in 111 families: results of an international study. | Neuhausen SL | American journal of human genetics | 1998 | PMID: 9585613 |
BRCA2 in American families with four or more cases of breast or ovarian cancer: recurrent and novel mutations, variable expression, penetrance, and the possibility of families whose cancer is not attributable to BRCA1 or BRCA2. | Schubert EL | American journal of human genetics | 1997 | PMID: 9150150 |
Mutations of the BRCA2 gene in ovarian carcinomas. | Takahashi H | Cancer research | 1996 | PMID: 8665505 |
click to load more click to collapse |
Text-mined citations for rs80359306 ...
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.