Variant allele predicted to encode a truncated non-functional protein.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.2612_2613insT (p.Phe872fs)
Germline
Reviewed by expert panel
Help
Reviewed by expert panel. Learn more about how ClinVar calculates review status.
Pathogenic
for
Breast-ovarian cancer, familial, susceptibility to, 1
Classification is based on the expert panel submission
Sep 2016 by
Evidence-based Network for the Interpretation of Germline M…
Help
The classification is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.2612_2613insT (p.Phe872fs)
Variation ID: 54619 Accession: VCV000054619.8
- Type and length
-
Insertion, 1 bp
- Location
-
Cytogenetic: 17q21.31 17: 43092918-43092919 (GRCh38) [ NCBI UCSC ] 17: 41244935-41244936 (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 May 1, 2024 Sep 8, 2016 - HGVS
- ... more HGVS ... less HGVS
- Protein change
- F825fs, F872fs, F744fs, F745fs, F831fs, F846fs, F704fs, F845fs, F576fs, F760fs, F784fs, F801fs, F802fs, F804fs, F830fs, F761fs, F783fs, F805fs, F824fs, F869fs, F871fs
- Other names
-
2731insT
- Canonical SPDI
- NC_000017.11:43092918::A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
- -
- Links
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. |
|||
| BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
13487 | 15382 | |
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 (3) |
reviewed by expert panel
|
Sep 8, 2016 | RCV000111904.13 | |
| Pathogenic (1) |
no assertion criteria provided
|
Jan 31, 2014 | RCV000496494.9 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Oct 27, 2017 | RCV000758801.11 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Sep 10, 2020 | RCV002426604.9 |
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
(Sep 08, 2016)
C
Contributing to aggregate classification
|
reviewed by expert panel
Method: curation
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000299796.2
First in ClinVar: Sep 24, 2016 Last updated: Sep 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
|
|
|
Pathogenic
(Oct 27, 2017)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000887649.2
First in ClinVar: Mar 14, 2019 Last updated: Jan 03, 2022 |
|
|
|
Pathogenic
(Oct 02, 2015)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge
Accession: SCV000325408.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
|
|
|
Pathogenic
(Sep 10, 2020)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002740736.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.2612_2613insT pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from an insertion of one nucleotide at position 2612, causing a … (more)
The c.2612_2613insT pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from an insertion of one nucleotide at position 2612, causing a translational frameshift with a predicted alternate stop codon (p.F872Vfs*31). This alteration has been seen in multiple patients with personal or family histories of breast and/or ovarian cancer (Gayther SA et al. Am. J. Hum. Genet. 1999 Oct;65(4):1021-9; Castéra L et al. Eur. J. Hum. Genet. 2014 Nov;22(11):1305-13). Of note, this alteration is also designated as 2731insT in some 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
(Jan 07, 2014)
N
Not contributing to aggregate classification
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
|
Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000144493.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 9
Observation 2:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: France
|
|
|
Pathogenic
(Jan 31, 2014)
N
Not contributing to aggregate classification
|
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: SCV000587238.1 First in ClinVar: Aug 07, 2017 Last updated: Aug 07, 2017 |
|
|
Comment:
Comment:
The c.2612_2613insT pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from an insertion of one nucleotide at position 2612, causing a translational frameshift with a predicted alternate stop codon (p.F872Vfs*31). This alteration has been seen in multiple patients with personal or family histories of breast and/or ovarian cancer (Gayther SA et al. Am. J. Hum. Genet. 1999 Oct;65(4):1021-9; Castéra L et al. Eur. J. Hum. Genet. 2014 Nov;22(11):1305-13). Of note, this alteration is also designated as 2731insT in some 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.
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. |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
Comment:
The c.2612_2613insT pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from an insertion of one nucleotide at position 2612, causing a translational frameshift with a predicted alternate stop codon (p.F872Vfs*31). This alteration has been seen in multiple patients with personal or family histories of breast and/or ovarian cancer (Gayther SA et al. Am. J. Hum. Genet. 1999 Oct;65(4):1021-9; Castéra L et al. Eur. J. Hum. Genet. 2014 Nov;22(11):1305-13). Of note, this alteration is also designated as 2731insT in some 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.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Next-generation sequencing for the diagnosis of hereditary breast and ovarian cancer using genomic capture targeting multiple candidate genes. | Castéra L | European journal of human genetics : EJHG | 2014 | PMID: 24549055 |
| The contribution of germline BRCA1 and BRCA2 mutations to familial ovarian cancer: no evidence for other ovarian cancer-susceptibility genes. | Gayther SA | American journal of human genetics | 1999 | PMID: 10486320 |
| Mutations and polymorphisms in the familial early-onset breast cancer (BRCA1) gene. Breast Cancer Information Core. | Couch FJ | Human mutation | 1996 | PMID: 8807330 |
Text-mined citations for rs80357948 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated May 17, 2025
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.