NM_000059.4(BRCA2):c.9117G>A (p.Pro3039=) AND Breast-ovarian cancer, familial, susceptibility to, 2
- Germline classification:
- Pathogenic (14 submissions)
- Last evaluated:
- Nov 9, 2023
- Review status:
- 3 stars out of maximum of 4 starsreviewed by expert panel
- Somatic classification
of clinical impact: - None
- Review status:
- (0/4) 0 stars out of maximum of 4 starsno assertion criteria provided
- Somatic classification
of oncogenicity: - None
- Review status:
- (0/4) 0 stars out of maximum of 4 starsno assertion criteria provided
- Record status:
- current
- Accession:
- RCV000031798.30
Allele description [Variation Report for NM_000059.4(BRCA2):c.9117G>A (p.Pro3039=)]
NM_000059.4(BRCA2):c.9117G>A (p.Pro3039=)
- Gene:
- BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]
- Variant type:
- single nucleotide variant
- Cytogenetic location:
- 13q13.1
- Genomic location:
- Preferred name:
- NM_000059.4(BRCA2):c.9117G>A (p.Pro3039=)
- Other names:
- P3039P; p.P3039P:CCG>CCA; NM_000059.4(BRCA2):c.9117G>A; p.Pro3039=
- HGVS:
- NC_000013.11:g.32379913G>A
- NG_012772.3:g.69434G>A
- NM_000059.4:c.9117G>AMANE SELECT
- NP_000050.2:p.Pro3039=
- NP_000050.3:p.Pro3039=
- LRG_293t1:c.9117G>A
- LRG_293:g.69434G>A
- LRG_293p1:p.Pro3039=
- NC_000013.10:g.32954050G>A
- NM_000059.3:c.9117G>A
- U43746.1:n.9345G>A
- p.P3039P
This HGVS expression did not pass validation- Nucleotide change:
- 9345G>A
- Links:
- dbSNP: rs28897756
- NCBI 1000 Genomes Browser:
- rs28897756
- Molecular consequence:
- NM_000059.4:c.9117G>A - synonymous variant - [Sequence Ontology: SO:0001819]
- Observations:
- 67
Condition(s)
Assertion and evidence details
Submission Accession | Submitter | Review Status (Assertion method) | Clinical Significance (Last evaluated) | Origin | Method | Citations |
---|---|---|---|---|---|---|
SCV000054406 | Sharing Clinical Reports Project (SCRP) | no assertion criteria provided | Pathogenic (Aug 31, 2013) | germline | clinical testing | |
SCV000147546 | Breast Cancer Information Core (BIC) (BRCA2) | no assertion criteria provided | Pathogenic (Feb 20, 2004) | germline, unknown | clinical testing | |
SCV000328057 | Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge | criteria provided, single submitter (CIMBA Mutation Classification guidelines May 2016) | Pathogenic (Oct 2, 2015) | germline | clinical testing | CIMBA_Mutation_Classification_guidelines_May16.pdf, |
SCV000488254 | Counsyl | criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015)) | Pathogenic (Feb 3, 2016) | unknown | clinical testing | PubMed (5) Counsyl Autosomal Dominant Disease Classification criteria (2015), |
SCV000575743 | Fulgent Genetics, Fulgent Genetics | criteria provided, single submitter (ACMG Guidelines, 2015) | Pathogenic (Sep 18, 2015) | unknown | clinical testing | |
SCV000605690 | Department of Medical Genetics, Oslo University Hospital | criteria provided, single submitter (ACMG Guidelines, 2015) | Pathogenic (Nov 2, 2015) | germline | clinical testing | |
SCV000733331 | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus | no assertion criteria provided | Pathogenic | germline | clinical testing | |
SCV000743359 | Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus | criteria provided, single submitter (ACGS Guidelines, 2013) | Pathogenic (Oct 10, 2014) | germline | clinical testing | |
SCV000744555 | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus | criteria provided, single submitter (ACGS Guidelines, 2013) | Pathogenic (Sep 21, 2015) | germline | clinical testing | |
SCV000839919 | Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine | criteria provided, single submitter (ACMG Guidelines, 2015) | Pathogenic (May 25, 2017) | germline | clinical testing | |
SCV001139248 | Mendelics | criteria provided, single submitter (Mendelics Assertion Criteria 2017) | Pathogenic (May 28, 2019) | unknown | clinical testing | |
SCV001251960 | Genomic Research Center, Shahid Beheshti University of Medical Sciences | criteria provided, single submitter (ACMG Guidelines, 2015) | Pathogenic (May 3, 2020) | unknown | clinical testing | |
SCV002588935 | BRCAlab, Lund University | no assertion criteria provided | Pathogenic (Aug 26, 2022) | germline | clinical testing | |
SCV004846127 | All of Us Research Program, National Institutes of Health | criteria provided, single submitter (ACMG Guidelines, 2015) | Pathogenic (Nov 9, 2023) | germline | clinical testing |
Summary from all submissions
Ethnicity | Origin | Affected | Individuals | Families | Chromosomes tested | Number Tested | Family history | Method |
---|---|---|---|---|---|---|---|---|
not provided | germline | not provided | 9 | not provided | not provided | 9 | not provided | clinical testing |
not provided | germline | unknown | 4 | 66 | not provided | 108544 | not provided | clinical testing |
not provided | germline | yes | 9 | 1 | not provided | not provided | not provided | clinical testing |
not provided | not provided | yes | 1 | not provided | not provided | not provided | not provided | clinical testing |
not provided | unknown | yes | not provided | not provided | not provided | not provided | not provided | clinical testing |
not provided | unknown | unknown | not provided | not provided | not provided | not provided | not provided | clinical testing |
African | germline | yes | 2 | not provided | not provided | not provided | not provided | clinical testing |
Ashkenazi | germline | yes | 1 | not provided | not provided | not provided | not provided | clinical testing |
Caucasian | germline | yes | 1 | not provided | not provided | not provided | not provided | clinical testing |
Western European | germline | yes | 4 | not provided | not provided | not provided | not provided | clinical testing |
Western European, Italian | germline | yes | 1 | not provided | not provided | not provided | not provided | clinical testing |
Citations
PubMed
Comprehensive splicing functional analysis of DNA variants of the BRCA2 gene by hybrid minigenes.
Acedo A, Sanz DJ, Durán M, Infante M, Pérez-Cabornero L, Miner C, Velasco EA.
Breast Cancer Res. 2012 May 25;14(3):R87.
- PMID:
- 22632462
- PMCID:
- PMC3446350
Zhang S, Royer R, Li S, McLaughlin JR, Rosen B, Risch HA, Fan I, Bradley L, Shaw PA, Narod SA.
Gynecol Oncol. 2011 May 1;121(2):353-7. doi: 10.1016/j.ygyno.2011.01.020. Epub 2011 Feb 15.
- PMID:
- 21324516
Details of each submission
From Sharing Clinical Reports Project (SCRP), SCV000054406.5
# | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
---|---|---|---|---|---|---|
1 | not provided | not provided | not provided | not provided | clinical testing | not provided |
# | Sample | Method | Observation | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
1 | germline | not provided | 9 | not provided | not provided | not provided | not provided | not provided | not provided |
From Breast Cancer Information Core (BIC) (BRCA2), SCV000147546.2
# | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
---|---|---|---|---|---|---|
1 | not provided | 4 | not provided | not provided | clinical testing | not provided |
2 | not provided | 1 | not provided | not provided | clinical testing | not provided |
3 | African | 2 | not provided | not provided | clinical testing | not provided |
4 | Ashkenazi | 1 | not provided | not provided | clinical testing | not provided |
5 | Caucasian | 1 | not provided | not provided | clinical testing | not provided |
6 | Western European | 4 | not provided | not provided | clinical testing | not provided |
7 | Western European, Italian | 1 | not provided | not provided | clinical testing | not provided |
# | Sample | Method | Observation | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
1 | germline | yes | not provided | not provided | not provided | 4 | not provided | not provided | not provided | |
2 | unknown | yes | not provided | not provided | not provided | 1 | not provided | not provided | not provided | |
3 | germline | yes | not provided | not provided | not provided | 2 | not provided | not provided | not provided | |
4 | germline | yes | not provided | not provided | not provided | 1 | not provided | not provided | not provided | |
5 | germline | yes | not provided | not provided | not provided | 1 | not provided | not provided | not provided | |
6 | germline | yes | not provided | not provided | not provided | 4 | not provided | not provided | not provided | |
7 | germline | yes | not provided | not provided | not provided | 1 | not provided | not provided | not provided |
From Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge, SCV000328057.4
# | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
---|---|---|---|---|---|---|
1 | not provided | not provided | not provided | not provided | clinical testing | not provided |
# | Sample | Method | Observation | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
1 | germline | unknown | not provided | not provided | not provided | not provided | not provided | 66 | not provided |
From Counsyl, SCV000488254.2
# | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
---|---|---|---|---|---|---|
1 | not provided | not provided | not provided | not provided | clinical testing | PubMed (5) |
# | Sample | Method | Observation | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
1 | unknown | unknown | not provided | not provided | not provided | not provided | not provided | not provided | not provided |
From Fulgent Genetics, Fulgent Genetics, SCV000575743.1
# | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
---|---|---|---|---|---|---|
1 | not provided | not provided | not provided | not provided | clinical testing | PubMed (1) |
# | Sample | Method | Observation | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
1 | unknown | unknown | not provided | not provided | not provided | not provided | not provided | not provided | not provided |
From Department of Medical Genetics, Oslo University Hospital, SCV000605690.3
# | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
---|---|---|---|---|---|---|
1 | not provided | 5 | not provided | not provided | clinical testing | PubMed (1) |
# | Sample | Method | Observation | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
1 | germline | yes | not provided | not provided | not provided | 5 | not provided | not provided | not provided |
From Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus, SCV000733331.1
# | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
---|---|---|---|---|---|---|
1 | not provided | not provided | not provided | not provided | clinical testing | not provided |
# | Sample | Method | Observation | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
1 | germline | yes | not provided | not provided | not provided | not provided | not provided | not provided | not provided |
From Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus, SCV000743359.1
# | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
---|---|---|---|---|---|---|
1 | not provided | not provided | not provided | not provided | clinical testing | not provided |
# | Sample | Method | Observation | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
1 | germline | yes | not provided | not provided | not provided | not provided | not provided | not provided | not provided |
From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV000744555.1
# | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
---|---|---|---|---|---|---|
1 | not provided | not provided | not provided | not provided | clinical testing | not provided |
# | Sample | Method | Observation | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
1 | germline | yes | not provided | not provided | not provided | not provided | not provided | not provided | not provided |
From Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine, SCV000839919.1
# | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
---|---|---|---|---|---|---|
1 | not provided | not provided | not provided | not provided | clinical testing | PubMed (1) |
Description
The c.9117G>A (p.Pro3039Pro) variant in the BRCA2 gene has been detected in multiple patients and families with breast and/or ovarian cancer [PMID 10638982 reported as 3398delAAAAG, 27000661] and a cohort of patients with prostate cancer [PMID 23035815, reported as c.9117 G>A (p.Val2985fs)]. The nucleotide position 9117 is the last nucleotide of exon 23. Several in vitro assays showed that the change leads aberrant splicing and the skipping of exon 23 [PMID 22505045, 23451180]. This variant is thus predicted to result in a loss of function of the protein. This variant has not been reported in the ExAC database. This variant thus classified as pathogenic.
# | Sample | Method | Observation | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
1 | germline | unknown | not provided | not provided | not provided | not provided | not provided | not provided | not provided |
From Mendelics, SCV001139248.1
# | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
---|---|---|---|---|---|---|
1 | not provided | not provided | not provided | not provided | clinical testing | not provided |
# | Sample | Method | Observation | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
1 | unknown | unknown | not provided | not provided | not provided | not provided | not provided | not provided | not provided |
From Genomic Research Center, Shahid Beheshti University of Medical Sciences, SCV001251960.1
# | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
---|---|---|---|---|---|---|
1 | not provided | not provided | not provided | not provided | clinical testing | PubMed (1) |
# | Sample | Method | Observation | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
1 | unknown | yes | not provided | not provided | not provided | not provided | not provided | not provided | not provided |
From BRCAlab, Lund University, SCV002588935.1
# | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
---|---|---|---|---|---|---|
1 | not provided | not provided | not provided | not provided | clinical testing | not provided |
# | Sample | Method | Observation | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
1 | germline | yes | not provided | not provided | not provided | not provided | not provided | 1 | not provided |
From All of Us Research Program, National Institutes of Health, SCV004846127.1
# | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
---|---|---|---|---|---|---|
1 | not provided | 4 | not provided | not provided | clinical testing | PubMed (19) |
Description
This variant changes a conserved and the last nucleotide in exon 23, and it is predicted to disrupt the intron 23 splice donor site. RNA studies have shown that this variant impacts splicing resulting in exon 23 skipping and introducing premature stop (PMID: 22505045, 23451180, 25382762, 27060066, 31843900, 32393398). This variant is expected to result in an absent or non-functional protein product. This variant has been reported in at least 10 individuals affected with breast or ovarian cancer (PMID: 18821011, 22798144, 24156927, 24249303, 25480878, 25556971, 25948282, 26026974, 27000661, 28477318, 28724667, 30287823). This variant has been identified in 1/248378 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.
# | Sample | Method | Observation | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
1 | germline | unknown | 108544 | not provided | not provided | 4 | not provided | not provided | not provided |
Last Updated: Nov 3, 2024