ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.3700_3704del (p.Val1234fs)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.3700_3704del (p.Val1234fs)
Variation ID: 37542 Accession: VCV000037542.88
- Type and length
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Microsatellite, 5 bp
- Location
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Cytogenetic: 17q21.31 17: 43091827-43091831 (GRCh38) [ NCBI UCSC ] 17: 41243844-41243848 (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 Aug 25, 2024 Apr 22, 2016 - HGVS
- ... more HGVS ... less HGVS
- Protein change
- V1234fs, V1187fs, V1122fs, V1145fs, V1186fs, V1207fs, V1231fs, V1066fs, V1166fs, V1233fs, V1106fs, V1123fs, V1163fs, V1193fs, V366fs, V1107fs, V1146fs, V1164fs, V1167fs, V1192fs, V1208fs, V938fs
- Other names
- 3819_3823delGTAAA
- 3819del5
- Canonical SPDI
- NC_000017.11:43091826:TTTACTTTAC:TTTAC
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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
Help
The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
13013 | 14815 | |
LOC126862571 | - | - | - | GRCh38 | - | 1649 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (14) |
reviewed by expert panel
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Apr 22, 2016 | RCV000031123.30 | |
Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Jan 9, 2024 | RCV000048287.28 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Nov 1, 2023 | RCV000131816.20 | |
Pathogenic (10) |
criteria provided, multiple submitters, no conflicts
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Feb 6, 2024 | RCV000235915.42 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 9, 2021 | RCV000238864.12 | |
Pathogenic (1) |
no assertion criteria provided
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Dec 1, 2018 | RCV000785409.10 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 26, 2019 | RCV001000425.15 | |
Pathogenic (1) |
no assertion criteria provided
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- | RCV001353692.9 | |
Pathogenic (1) |
no assertion criteria provided
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Aug 16, 2021 | RCV001564012.9 | |
Pathogenic (1) |
no assertion criteria provided
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Jun 11, 2019 | RCV001271015.9 | |
Pathogenic (1) |
no assertion criteria provided
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Aug 21, 2021 | RCV001579304.9 | |
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Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Apr 22, 2016)
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reviewed by expert panel
Method: curation
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
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Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000282314.1
First in ClinVar: Jun 24, 2016 Last updated: Jun 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
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Pathogenic
(Dec 15, 2015)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
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Department of Medical Genetics, Oslo University Hospital
Accession: SCV000564379.1
First in ClinVar: Apr 22, 2017 Last updated: Apr 22, 2017 |
Number of individuals with the variant: 7
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Pathogenic
(May 26, 2017)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000699059.1
First in ClinVar: Dec 26, 2017 Last updated: Dec 26, 2017 |
Comment:
Variant summary: The c.3700_3704delGTAAA (p.Val1234Glnfs) variant in BRCA1 gene is a frameshift change that is predicted to cause loss of normal protein function through protein … (more)
Variant summary: The c.3700_3704delGTAAA (p.Val1234Glnfs) variant in BRCA1 gene is a frameshift change that is predicted to cause loss of normal protein function through protein truncation or nonsense-mediated mRNA decay. The variant is absent from the large control population datasets of ExAC and gnomAD (~121382 and 246014 chrs tested). The variant of interest has been reported in multiple affected individuals and was shown to segregate with the disease within the family. Multiple reputable databases/clinical laboratories and published reports cited the variant as pathogenic. Taking together, the variant was classified as Pathogenic. (less)
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Pathogenic
(Jan 13, 2017)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
(Autosomal dominant inheritance)
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000605765.2
First in ClinVar: Aug 27, 2017 Last updated: Dec 26, 2017 |
Comment:
The p.Val1234fs variant in BRCA1 has been reported in >60 individuals with BRCA1 -associated cancers (Brozek 2011, Ratajska 2015, Breast Cancer Information Core (BIC)), and … (more)
The p.Val1234fs variant in BRCA1 has been reported in >60 individuals with BRCA1 -associated cancers (Brozek 2011, Ratajska 2015, Breast Cancer Information Core (BIC)), and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 1234 and leads to a premature termination codon 8 amino acids downst ream. This alteration is then predicted to lead to a truncated or absent protein . Heterozygous loss of function of function of the BRCA1 gene is an established disease mechanism in hereditary breast and ovarian cancer (HBOC). In addition, this variant was classified as Pathogenic on April 22, 2016 by the ClinGen-appro ved ENIGMA expert panel (ClinVar SCV000282314.1). In summary, the p.Val1234fs va riant meets criteria to be classified as pathogenic for HBOC in an autosomal dom inant manner. (less)
Number of individuals with the variant: 1
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Pathogenic
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001140547.1
First in ClinVar: Jan 13, 2020 Last updated: Jan 13, 2020 |
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Pathogenic
(Jul 15, 2014)
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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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Clinical Genetics and Genomics, Karolinska University Hospital
Accession: SCV001450231.1
First in ClinVar: Dec 12, 2020 Last updated: Dec 12, 2020 |
Number of individuals with the variant: 1
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Pathogenic
(Jul 28, 2022)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
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MGZ Medical Genetics Center
Accession: SCV002581454.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PVS1, PP1_STR, PS4_MOD, PM2_SUP
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Number of individuals with the variant: 3
Sex: female
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Pathogenic
(Sep 24, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000600345.4
First in ClinVar: Sep 28, 2017 Last updated: Jan 06, 2024 |
Comment:
This frameshift variant causes the premature termination of BRCA1 protein synthesis. In the published literature, it has been reported in patients with breast/ovarian cancer and … (more)
This frameshift variant causes the premature termination of BRCA1 protein synthesis. In the published literature, it has been reported in patients with breast/ovarian cancer and is described as a common mutation in individuals with Polish ancestry (PMID: 29335924 (2018), 28205045 (2017), 26843898 (2016), 22535016 (2012), 21324516 (2011)). Based on the available information, this variant is classified as pathogenic. (less)
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Pathogenic
(Aug 19, 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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Ambry Genetics
Accession: SCV000186871.8
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
The c.3700_3704delGTAAA pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of 5 nucleotides at nucleotide positions 3700 to … (more)
The c.3700_3704delGTAAA pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of 5 nucleotides at nucleotide positions 3700 to 3704, causing a translational frameshift with a predicted alternate stop codon (p.V1234Qfs*8). This mutation has been reported in multiple hereditary breast and ovarian cancer (HBOC) syndrome families (Takahashi H et al. Cancer Res., 1995 Jul;55:2998-3002; Serova O et al. Am J Hum Genet, 1996 Jan;58:42-51; Górski B et al. Am J Hum Genet, 2000 Jun;66:1963-8; Bergthorsson JT et al. J Med Genet, 2001 Jun;38:361-8; Foretova L et al. Hum Mutat, 2004 Apr;23:397-8; Ratajska M et al. Oncol Rep, 2008 Jan;19:263-8; Machackova E et al. BMC Cancer, 2008 May;8:140; Iyevleva AG et al. Cancer Lett, 2010 Dec;298:258-63; Zhang S et al. Gynecol Oncol, 2011 May;121:353-7; Heidemann S et al. Breast Cancer Res Treat, 2012 Aug;134:1229-39; Ledwo JK et al. BMC Cancer, 2013 Oct;13:510; de Juan Jiménez I et al. Fam Cancer, 2013 Dec;12:767-77; Janaviius R et al. Cancer Genet, 2014 May;207:195-205; Meisel C et al. Arch Gynecol Obstet, 2017 May;295:1227-1238; Park B et al. Breast Cancer Res Treat, 2017 May;163:139-150; Zidekova D et al. Neoplasma;65:309-315; Heramb C et al. Hered Cancer Clin Pract, 2018 Jan;16:3; Li A et al. Gynecol Oncol, 2018 10;151:145-152; Jakimovska M et al. Breast Cancer Res Treat, 2018 Apr;168:745-753; Rechsteiner M et al. J. Cancer Res. Clin. Oncol., 2018 May;144:865-874; Kluz T et al. Hered Cancer Clin Pract, 2018 Mar;16:6; Carter NJ et al. Gynecol Oncol, 2018 12;151:481-488; Koczkowska M et al. Cancers (Basel), 2018 Nov;10; Tsaousis GN et al. BMC Cancer, 2019 Jun;19:535; Rashid MU et al. Hered Cancer Clin Pract, 2019 Sep;17:27; Rogoa-Janiszewska E et al. Cancers (Basel), 2020 Aug;12; Yildiz Tacar S et al. Life Sci, 2020 Nov;261:118334; Zografos E et al. BMC Cancer, 2021 May;21:572). This mutation has also been reported in a case study of a 74-year old male patient with a metastasized combined adeno-neuroendocrine carcinomas (MANEC) of the small bowel (Quaas A et al. BMC Gastroenterol, 2018 May;18:75). Of note, this alteration is also designated as c.3700_3704del5, 3819del5, and "3820-3824 5bp deletion" in 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)
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Pathogenic
(Apr 26, 2019)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001157235.1
First in ClinVar: Feb 10, 2020 Last updated: Feb 10, 2020 |
Comment:
The BRCA1 c.3700_3704del; p.Val1234fs variant (rs80357609), also known as 3819del5, is reported in the literature in multiple individuals and families affected with hereditary breast and … (more)
The BRCA1 c.3700_3704del; p.Val1234fs variant (rs80357609), also known as 3819del5, is reported in the literature in multiple individuals and families affected with hereditary breast and ovarian cancer, and is described as a recurrent BRCA1 variant in Eastern European individuals (Brozek 2011, Foretova 2004, Gorski 2000, Heramb 2018, Konstantopoulou 2014, Machackova 2008, Ratajska 2008, Takahashi 1995). This variant is reported as pathogenic by multiple laboratories in ClinVar (Variation ID: 37542), and is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant causes a frameshift by deleting 5 nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Brozek I et al. Prevalence of the most frequent BRCA1 mutations in Polish population. J Appl Genet. 2011 Aug;52(3):325-30. Foretova L 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):397-8. Gorski B et al. Founder mutations in the BRCA1 gene in Polish families with breast-ovarian cancer. Am J Hum Genet. 2000 Jun;66(6):1963-8. Heramb C et al. BRCA1 and BRCA2 mutation spectrum - an update on mutation distribution in a large cancer genetics clinic in Norway. Hered Cancer Clin Pract. 2018 Jan 10;16:3. Konstantopoulou I et al. High prevalence of BRCA1 founder mutations in Greek breast/ovarian families. Clin Genet. 2014 Jan;85(1):36-42. Machackova E et al. Spectrum and characterisation of BRCA1 and BRCA2 deleterious mutations in high-risk Czech patients with breast and/or ovarian cancer. BMC Cancer. 2008 May 20;8:140. Ratajska M et al. BRCA1 and BRCA2 point mutations and large rearrangements in breast and ovarian cancer families in Northern Poland. Oncol Rep. 2008 Jan;19(1):263-8. Takahashi H et al. Mutation analysis of the BRCA1 gene in ovarian cancers. Cancer Res. 1995 Jul 15;55(14):2998-3002. (less)
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Pathogenic
(Jan 09, 2021)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: yes
Allele origin:
germline
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GeneKor MSA
Accession: SCV000296798.4
First in ClinVar: Aug 01, 2016 Last updated: Oct 02, 2021 |
Comment:
This sequence change deletes 5 nucleotides in exon 11 of BRCA1 mRNA (c.3700_3704delGTAAA), causing a frameshift at codon 1234 and the creation of a premature … (more)
This sequence change deletes 5 nucleotides in exon 11 of BRCA1 mRNA (c.3700_3704delGTAAA), causing a frameshift at codon 1234 and the creation of a premature translation stop signal 8 amino acid residues later p.(Val1234Glnfs*8). This is expected to result in an absent or disrupted protein product. Truncating variants in BRCA1 are known to be pathogenic.This sequence change has been reported in the international literature in multiple families with Hereditary Breast and Ovarian Cancer syndrome and has been suggested to be a common BRCA1 variant in the Czech Republic (PMID: 15024741 ;22160602 ).This mutation has been described in the mutation database ClinVar (Variation ID: 37542). (less)
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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, 1
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: SCV000325727.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
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Pathogenic
(Mar 03, 2016)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000488333.2
First in ClinVar: Nov 05, 2016 Last updated: Dec 24, 2022 |
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Pathogenic
(Oct 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004212743.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Feb 08, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: unknown
Allele origin:
germline
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV004224883.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
PP1, PM2, PS4_moderate, PVS1
Number of individuals with the variant: 1
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Pathogenic
(Apr 21, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV003811733.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Pathogenic
(Nov 01, 2023)
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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: SCV000683123.4
First in ClinVar: Feb 19, 2018 Last updated: Feb 14, 2024 |
Comment:
This variant deletes 5 nucleotides in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is expected to … (more)
This variant deletes 5 nucleotides in exon 10 of the BRCA1 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 is also known as 3819del5 based on Breast Cancer Information Core (BIC) nomenclature. This variant has been detected in multiple individuals and families affected with breast and ovarian cancer (PMID: 7606717, 8554067, 11389159, 11802209 , 18489799, 20727672, 21324516, 23479189, 24171766, 24010542, 25366421, 28205045, 29335924, 33670479, 34072659) and has been described as a recurrent or founder mutation in the Czech Republic, Germany, Poland, Kosovo and Russia (PMID: 22864640, 23199084, 26843898, 36171877, 36299383, 36367610, 37147448). This variant was found to segregate with breast and ovarian cancer affected members in one large pedigree (PMID: 8554067). A large breast cancer case-control study (PMID: 33471991) has reported this variant in 10/60456 cases, 1/53460 controls; OR=8.843 (95%CI 1.132 to 69.082); p-value=0.013; Leiden Open Variation Database DB-ID BRCA1_001454. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 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
(Apr 18, 2017)
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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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Cancer Genetics and Genomics Laboratory, British Columbia Cancer Agency
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000586894.1 First in ClinVar: Apr 16, 2017 Last updated: Apr 16, 2017 |
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Pathogenic
(Feb 01, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001480186.1
First in ClinVar: Feb 20, 2021 Last updated: Feb 20, 2021 |
Clinical Features:
Breast carcinoma (present)
Sex: female
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Pathogenic
(Sep 13, 2018)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001429221.2
First in ClinVar: Aug 17, 2020 Last updated: Jul 31, 2021 |
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Pathogenic
(Jun 16, 2021)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002538230.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Comment:
The BRCA1 c.3700_3704delGTAAA (p.V1234QfsX8) variant has been reported in heterozygosity in at least 22 individuals with a personal or family history of breast and/or ovarian … (more)
The BRCA1 c.3700_3704delGTAAA (p.V1234QfsX8) variant has been reported in heterozygosity in at least 22 individuals with a personal or family history of breast and/or ovarian cancer (PMIDs: 7606717, 15024741, 18097605, 21324516, 29339979) and in 1 individual with mixed adeno-neuroendocrine carcinoma (MANEC) of small bowel (PMID 29855275) among other reports. This variant causes a frameshift at amino acid 1234 that results in premature termination 8 amino acids downstream. At this location, this is predicted to cause nonsense-mediated decay and result in an absent protein (loss of function). Loss of function variants in BRCA1 or BRCA2 are known to be pathogenic (PMID: 29446198). This variant is not reported in the population database Genome Aggregation Database (http://gnomad.broadinstitute.org, PMID: 32461654). This variant has been reported in ClinVar (Variation ID: 37542). Based on the current evidence available, this variant is interpreted as pathogenic. (less)
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Pathogenic
(Nov 17, 2021)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000292517.14
First in ClinVar: Jul 24, 2016 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 syndrome and described as a recurrent variant in Eastern European individuals (Foretova 2004, Foretova 2010, Schneegans 2012, de Juan Jimenez 2013, Ratajska 2015); Not observed at significant frequency in large population cohorts (Lek 2016); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 3695_3699delGTAAA, 3819_3823delGTAAA, and 3819del5; This variant is associated with the following publications: (PMID: 26843898, 25452441, 21324516, 7606717, 21503673, 22535016, 26083025, 10952777, 23479189, 15024741, 21348412, 27167707, 28205045, 25366421, 22160602, 27836010, 24171766, 29339979, 29335924, 28324225, 30322717, 31159747, 18097605, 30702160, 30078507, 31528241, 32719484, 32846166, 32341426, 31742824, 32295079, 34011307) (less)
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Pathogenic
(Nov 03, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002009450.3
First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023 |
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Pathogenic
(Feb 06, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV004242820.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
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Pathogenic
(Jan 09, 2024)
|
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: SCV000076300.13
First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Val1234Glnfs*8) in the BRCA1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Val1234Glnfs*8) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 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 breast and/or ovarian cancer (PMID: 15024741, 18489799, 21324516, 23479189, 24010542, 25066507). This variant is also known as 3819del5. ClinVar contains an entry for this variant (Variation ID: 37542). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jan 08, 2024)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004817763.1
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)
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Comment:
This variant deletes 5 nucleotides in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is expected to … (more)
This variant deletes 5 nucleotides in exon 10 of the BRCA1 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 is also known as 3819del5 based on Breast Cancer Information Core (BIC) nomenclature. This variant has been detected in multiple individuals and families affected with breast and ovarian cancer (PMID: 7606717, 8554067, 11389159, 11802209 , 18489799, 20727672, 21324516, 23479189, 24171766, 24010542, 25366421, 28205045, 29335924, 33670479, 34072659) and has been described as a recurrent or founder mutation in the Czech Republic, Germany, Poland, Kosovo and Russia (PMID: 22864640, 23199084, 26843898, 36171877, 36299383, 36367610, 37147448). This variant was found to segregate with breast and ovarian cancer affected members in one large pedigree (PMID: 8554067). A large breast cancer case-control study (PMID: 33471991) has reported this variant in 10/60456 cases, 1/53460 controls; OR=8.843 (95%CI 1.132 to 69.082); p-value=0.013; Leiden Open Variation Database DB-ID BRCA1_001454. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 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: 1
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Pathogenic
(Jun 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics Laboratory, Skane University Hospital Lund
Accession: SCV005198128.1
First in ClinVar: Aug 25, 2024 Last updated: Aug 25, 2024 |
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Pathogenic
(Apr 02, 2020)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Department of Molecular Diagnostics, Institute of Oncology Ljubljana
Accession: SCV001499718.1
First in ClinVar: Mar 07, 2021 Last updated: Mar 07, 2021 |
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Pathogenic
(May 27, 2024)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet
Accession: SCV005045942.1
First in ClinVar: Jun 02, 2024 Last updated: Jun 02, 2024 |
Comment:
PVS1; PM2_supporting; PM5_PTC_Strong
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Pathogenic
(Nov 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001247353.23
First in ClinVar: May 12, 2020 Last updated: Aug 04, 2024 |
Comment:
BRCA1: PVS1, PM2, PP1
Number of individuals with the variant: 9
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Pathogenic
(May 01, 2012)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: not provided
Allele origin:
germline
|
Sharing Clinical Reports Project (SCRP)
Accession: SCV000053721.5
First in ClinVar: Apr 04, 2013 Last updated: Sep 27, 2014 |
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Pathogenic
(May 29, 2002)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
|
Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000144839.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 18
Observation 2:
Number of individuals with the variant: 1
Geographic origin: France
Observation 3:
Number of individuals with the variant: 1
Geographic origin: Germany
Observation 4:
Number of individuals with the variant: 2
Geographic origin: Western European
Observation 5:
Number of individuals with the variant: 2
Ethnicity/Population group: Caucasian
Observation 6:
Number of individuals with the variant: 24
Ethnicity/Population group: Caucasian
Geographic origin: Czech Republic
Observation 7:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: Denmark
Observation 8:
Number of individuals with the variant: 4
Ethnicity/Population group: Caucasian
Geographic origin: Germany
Observation 9:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: Italy
Observation 10:
Number of individuals with the variant: 1
Ethnicity/Population group: Central/Eastern European
Observation 11:
Number of individuals with the variant: 6
Ethnicity/Population group: Polish
Geographic origin: Poland
Observation 12:
Number of individuals with the variant: 10
Ethnicity/Population group: Western European
Observation 13:
Number of individuals with the variant: 1
Ethnicity/Population group: Western, Central/Eastern European
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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
|
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000587333.1 First in ClinVar: Apr 16, 2017 Last updated: Apr 16, 2017 |
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Pathogenic
(Aug 16, 2021)
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no assertion criteria provided
Method: clinical testing
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Abnormality of the ovary
Affected status: yes
Allele origin:
germline
|
Medical Genetics Laboratory, Umraniye Training and Research Hospital, University of Health Sciences
Accession: SCV001786709.1
First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
Age: 60-69 years
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Pathogenic
(Dec 01, 2018)
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no assertion criteria provided
Method: research
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Ovarian neoplasm
Affected status: yes
Allele origin:
germline
|
German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne
Accession: SCV000923981.1
First in ClinVar: Jun 17, 2019 Last updated: Jun 17, 2019 |
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Pathogenic
(Jun 11, 2019)
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no assertion criteria provided
Method: clinical testing
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Breast and/or ovarian cancer
Affected status: yes
Allele origin:
germline
|
CZECANCA consortium
Accession: SCV001451827.1
First in ClinVar: Dec 26, 2020 Last updated: Dec 26, 2020 |
Number of individuals with the variant: 30
Ethnicity/Population group: Slavic
Geographic origin: Czech Republic
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Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
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Malignant tumor of breast
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: SCV000591463.2 First in ClinVar: Aug 27, 2017 Last updated: Apr 13, 2021 |
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Pathogenic
(Aug 21, 2021)
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no assertion criteria provided
Method: clinical testing
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Ovarian carcinoma
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Medical Genetics Laboratory, Umraniye Training and Research Hospital, University of Health Sciences
Accession: SCV001805838.1
First in ClinVar: Aug 27, 2021 Last updated: Aug 27, 2021 |
Comment:
high grade serous carcinoma
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Pathogenic
(Aug 26, 2022)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
BRCAlab, Lund University
Accession: SCV002589109.1
First in ClinVar: Apr 01, 2023 Last updated: Apr 01, 2023 |
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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 |
---|---|---|---|---|
New, fast and cheap prediction tests for BRCA1 gene mutations identification in clinical samples. | Gajda-Walczak A | Scientific reports | 2023 | PMID: 37147448 |
A spectrum of BRCA1 and BRCA2 germline deleterious variants in ovarian cancer in Russia. | Kechin A | Breast cancer research and treatment | 2023 | PMID: 36367610 |
The highest frequency of BRCA1 c.3700_3704del detected among Albanians from Kosovo. | Kostovska IM | Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology | 2022 | PMID: 36299383 |
Detection of BRCA1/2 pathogenic variants in patients with breast and/or ovarian cancer and their families. Analysis of 3,458 cases from Lower Silesia (Poland) according to the diagnostic algorithm of the National Cancer Control Programme. | Doraczynska-Kowalik A | Frontiers in genetics | 2022 | PMID: 36171877 |
Evaluation of hereditary/familial breast cancer patients with multigene targeted next generation sequencing panel and MLPA analysis in Turkey. | Bora E | Cancer genetics | 2022 | PMID: 35220195 |
The detection of germline and somatic BRCA1/2 genetic variants through parallel testing of patients with high-grade serous ovarian cancer: a national retrospective audit. | Frugtniet B | BJOG : an international journal of obstetrics and gynaecology | 2022 | PMID: 34657373 |
Concurrent pathogenic variations in patients with hereditary cancer syndromes. | Agaoglu NB | European journal of medical genetics | 2021 | PMID: 34637943 |
Study of the Genetic Variants in BRCA1/2 and Non-BRCA Genes in a Population-Based Cohort of 2155 Breast/Ovary Cancer Patients, Including 443 Triple-Negative Breast Cancer Patients, in Argentina. | Solano AR | Cancers | 2021 | PMID: 34072659 |
Germline mutations in a clinic-based series of pregnancy associated breast cancer patients. | Zografos E | BMC cancer | 2021 | PMID: 34011307 |
Recurrent Mutations in BRCA1, BRCA2, RAD51C, PALB2 and CHEK2 in Polish Patients with Ovarian Cancer. | Łukomska A | Cancers | 2021 | PMID: 33670479 |
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 |
Next generation sequencing analysis of BRCA1 and BRCA2 identifies novel variations in breast cancer. | Yildiz Tacar S | Life sciences | 2020 | PMID: 32846166 |
Prevalence of Recurrent Mutations Predisposing to Breast Cancer in Early-Onset Breast Cancer Patients from Poland. | Rogoża-Janiszewska E | Cancers | 2020 | PMID: 32824581 |
Population genetic screening efficiently identifies carriers of autosomal dominant diseases. | Grzymski JJ | Nature medicine | 2020 | PMID: 32719484 |
Spectrum of Germline BRCA1 and BRCA2 Variants Identified in 2351 Ovarian and Breast Cancer Patients Referring to a Reference Cancer Hospital of Rome. | Santonocito C | Cancers | 2020 | PMID: 32438681 |
Clinical outcome of breast cancer in carriers of BRCA1 and BRCA2 mutations according to molecular subtypes. | De Talhouet S | Scientific reports | 2020 | PMID: 32341426 |
Prevalence of hereditary breast and ovarian cancer (HBOC) predisposition gene mutations among 882 HBOC high-risk Chinese individuals. | Shao D | Cancer science | 2020 | PMID: 31742824 |
Spectrum and prevalence of BRCA1/2 germline mutations in Pakistani breast cancer patients: results from a large comprehensive study. | Rashid MU | Hereditary cancer in clinical practice | 2019 | PMID: 31528241 |
Analysis of hereditary cancer syndromes by using a panel of genes: novel and multiple pathogenic mutations. | Tsaousis GN | BMC cancer | 2019 | PMID: 31159747 |
Spectrum and Prevalence of Pathogenic Variants in Ovarian Cancer Susceptibility Genes in a Group of 333 Patients. | Koczkowska M | Cancers | 2018 | PMID: 30441849 |
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 |
BRCA germline mutations in an unselected nationwide cohort of Chinese patients with ovarian cancer and healthy controls. | Li A | Gynecologic oncology | 2018 | PMID: 30078507 |
Therapy susceptible germline-related BRCA 1-mutation in a case of metastasized mixed adeno-neuroendocrine carcinoma (MANEC) of the small bowel. | Quaas A | BMC gastroenterology | 2018 | PMID: 29855275 |
Rapid screening test of most frequent BRCA1/BRCA2 pathogenic variants in the NGS era. | Zidekova D | Neoplasma | 2018 | PMID: 29534594 |
Frequency of BRCA1 and BRCA2 causative founder variants in ovarian cancer patients in South-East Poland. | Kluz T | Hereditary cancer in clinical practice | 2018 | PMID: 29492181 |
Somatic BRCA1 mutations in clinically sporadic breast cancer with medullary histological features. | Rechsteiner M | Journal of cancer research and clinical oncology | 2018 | PMID: 29453630 |
Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. | Rebbeck TR | Human mutation | 2018 | PMID: 29446198 |
BRCA1 and BRCA2 mutation spectrum - an update on mutation distribution in a large cancer genetics clinic in Norway. | Heramb C | Hereditary cancer in clinical practice | 2018 | PMID: 29339979 |
BRCA1 and BRCA2 germline variants in breast cancer patients from the Republic of Macedonia. | Jakimovska M | Breast cancer research and treatment | 2018 | PMID: 29335924 |
Frequency of mutations in a large series of clinically ascertained ovarian cancer cases tested on multi-gene panels compared to reference controls. | Lilyquist J | Gynecologic oncology | 2017 | PMID: 28888541 |
Spectrum of genetic variants of BRCA1 and BRCA2 in a German single center study. | Meisel C | Archives of gynecology and obstetrics | 2017 | PMID: 28324225 |
Characteristics of BRCA1/2 mutations carriers including large genomic rearrangements in high risk breast cancer patients. | Park B | Breast cancer research and treatment | 2017 | PMID: 28205045 |
Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women. | Rebbeck TR | Breast cancer research : BCR | 2016 | PMID: 27836010 |
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 |
Mutational analysis of BRCA1/2 in a group of 134 consecutive ovarian cancer patients. Novel and recurrent BRCA1/2 alterations detected by next generation sequencing. | Ratajska M | Journal of applied genetics | 2015 | PMID: 25366421 |
Comprehensive BRCA1 and BRCA2 mutational profile in Lithuania. | Janavičius R | Cancer genetics | 2014 | PMID: 25066507 |
High prevalence of BRCA1 founder mutations in Greek breast/ovarian families. | Konstantopoulou I | Clinical genetics | 2014 | PMID: 24010542 |
Common low-penetrance risk variants associated with breast cancer in Polish women. | Ledwoń JK | BMC cancer | 2013 | PMID: 24171766 |
Novel and recurrent BRCA1/BRCA2 mutations in early onset and familial breast and ovarian cancer detected in the Program of Genetic Counseling in Cancer of Valencian Community (eastern Spain). Relationship of family phenotypes with mutation prevalence. | de Juan Jiménez I | Familial cancer | 2013 | PMID: 23479189 |
High frequency of BRCA1 founder mutations in Polish women with nonfamilial breast cancer. | Gaj P | Familial cancer | 2012 | PMID: 22864640 |
BRCA1 regulates follistatin function in ovarian cancer and human ovarian surface epithelial cells. | Karve TM | PloS one | 2012 | PMID: 22685544 |
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 |
Validation of three BRCA1/2 mutation-carrier probability models Myriad, BRCAPRO and BOADICEA in a population-based series of 183 German families. | Schneegans SM | Familial cancer | 2012 | PMID: 22160602 |
A high-throughput protocol for mutation scanning of the BRCA1 and BRCA2 genes. | Hondow HL | BMC cancer | 2011 | PMID: 21702907 |
Prevalence of the most frequent BRCA1 mutations in Polish population. | Brozek I | Journal of applied genetics | 2011 | PMID: 21503673 |
Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer. | Zhang S | Gynecologic oncology | 2011 | PMID: 21324516 |
Founder BRCA1/2 mutations in the Europe: implications for hereditary breast-ovarian cancer prevention and control. | Janavičius R | The EPMA journal | 2010 | PMID: 23199084 |
Non-founder BRCA1 mutations in Russian breast cancer patients. | Iyevleva AG | Cancer letters | 2010 | PMID: 20727672 |
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 |
BRCA1 and BRCA2 point mutations and large rearrangements in breast and ovarian cancer families in Northern Poland. | Ratajska M | Oncology reports | 2008 | PMID: 18097605 |
Application of embryonic lethal or other obvious phenotypes to characterize the clinical significance of genetic variants found in trans with known deleterious mutations. | Judkins T | Cancer research | 2005 | PMID: 16267036 |
[Prevalence of widespread BRCA1 gene mutations in patients with familial breast cancer from St. Petersburg]. | Grudinina NA | Genetika | 2005 | PMID: 15865297 |
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 |
BRCA1 and BRCA2 mutation status and cancer family history of Danish women affected with multifocal or bilateral breast cancer at a young age. | Bergthorsson JT | Journal of medical genetics | 2001 | PMID: 11389159 |
Founder mutations in the BRCA1 gene in Polish families with breast-ovarian cancer. | Górski B | American journal of human genetics | 2000 | PMID: 10788334 |
A high incidence of BRCA1 mutations in 20 breast-ovarian cancer families. | Serova O | American journal of human genetics | 1996 | PMID: 8554067 |
Mutation analysis of the BRCA1 gene in ovarian cancers. | Takahashi H | Cancer research | 1995 | PMID: 7606717 |
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Text-mined citations for rs80357609 ...
HelpRecord last updated Aug 25, 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.