NM_000059.4(BRCA2):c.7069_7070del (p.Leu2357fs) AND Breast-ovarian cancer, familial, susceptibility to, 2

Germline classification:: Pathogenic (18 submissions)
Last evaluated:: Apr 22, 2016
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000031664.30

Allele description [Variation Report for NM_000059.4(BRCA2):c.7069_7070del (p.Leu2357fs)]

NM_000059.4(BRCA2):c.7069_7070del (p.Leu2357fs)

Gene:

BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.7069_7070del (p.Leu2357fs)

Other names:

2357delCT; 7297_7298delCT

HGVS:

NC_000013.10:g.32929058_32929059del
NC_000013.11:g.32354922_32354923del
NG_012772.3:g.44443_44444del
NM_000059.4:c.7069_7070delMANE SELECT
NP_000050.3:p.Leu2357fs
LRG_293:g.44443_44444del
NC_000013.10:g.32929058_32929059del
NC_000013.10:g.32929059_32929060del
NC_000013.10:g.32929059_32929060del
NC_000013.10:g.32929059_32929060delCT
NM_000059.3:c.7069_7070delCT
NM_000059.4:c.7069_7070del
NM_000059.4:c.7069_7070delCT
U43746.1:n.7297_7298delCT
p.L2357VFS*2
p.L2357VfsX2
p.Leu2357Valfs*2
p.Leu2357ValfsX2
p.Leu2357fs

Nucleotide change:

7297delCT

Links:

Breast Cancer Information Core (BIC) (BRCA2): 7297&base_change=del CT; dbSNP: rs80359636

NCBI 1000 Genomes Browser:

rs80359636

Molecular consequence:

NM_000059.4:c.7069_7070del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

100

Condition(s)

Name:: Breast-ovarian cancer, familial, susceptibility to, 2 (BROVCA2)
Synonyms:: Breast-ovarian cancer, familial 2
Identifiers:: MONDO: MONDO:0012933; MedGen: C2675520; Orphanet: 145; OMIM: 612555

Recent activity

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response regulator transcription factor [Streptococcus agalactiae]
response regulator transcription factor [Streptococcus agalactiae]
gi|446931368|ref|WP_001008624.1|

Protein
DUF4365 domain-containing protein [Streptococcus agalactiae]
DUF4365 domain-containing protein [Streptococcus agalactiae]
gi|446283771|ref|WP_000361626.1|

Protein
N-terminal EF-hand calcium-binding protein 3 isoform X3 [Mus musculus]
N-terminal EF-hand calcium-binding protein 3 isoform X3 [Mus musculus]
gi|1907142078|ref|XP_036018309.1|

Protein
PREDICTED: Homo sapiens integrin subunit alpha M (ITGAM), transcript variant X5,...
PREDICTED: Homo sapiens integrin subunit alpha M (ITGAM), transcript variant X5, mRNA
gi|2462548900|ref|XM_054380271.1|

Nucleotide
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000054271	Sharing Clinical Reports Project (SCRP)	no assertion criteria provided	Pathogenic (Apr 23, 2013)	germline	clinical testing
SCV000147015	Breast Cancer Information Core (BIC) (BRCA2)	no assertion criteria provided	Pathogenic (May 29, 2002)	germline	clinical testing
SCV000196001	Michigan Medical Genetics Laboratories, University of Michigan	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 3, 2014)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000282439	Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	reviewed by expert panel (ENIGMA BRCA1/2 Classification Criteria (2015))	Pathogenic (Apr 22, 2016)	germline	curation	ENIGMA BRCA1/2 Classification Criteria (2015), Citation Link,
SCV000327588	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, Citation Link,
SCV000488257	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Pathogenic (Feb 4, 2016)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21324516, 20104584, 22762150 Counsyl Autosomal Dominant Disease Classification criteria (2015), Citation Link,
SCV000577969	Genologica Medica See additional submitters Servicio Andaluz de Salud, Hospital Universitario Virgen de la Victoria	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 1, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000605676	Department of Medical Genetics, Oslo University Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 1, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000733293	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV000744510	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	Citation Link,
SCV000804428	Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 11, 2017)	maternal	provider interpretation, clinical testing	PubMed (7) [See all records that cite these PMIDs] 23628597, 20587410, 18042939, 16141007, 19188187, 18855126, 25741868
SCV001434856	Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 6, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002761530	Genetics and Molecular Pathology, SA Pathology See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 10, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004100706	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 5, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004243752	BRCAlab, Lund University	no assertion criteria provided	Pathogenic (Mar 2, 2020)	germline	clinical testing
SCV004844359	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 5, 2024)	germline	clinical testing	PubMed (12) [See all records that cite these PMIDs] 9667259, 16234499, 18824701, 20104584, 21324516, 21913181, 24504028, 24549055, 24728189, 27978560, 34700141, 25741868
SCV005045980	Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 27, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005049484	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 1, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	10	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	5	99	not provided	108544	not provided	clinical testing, curation
not provided	maternal	no	1	not provided	not provided	1	not provided	clinical testing, provider interpretation
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	30	not provided	not provided	30	not provided	clinical testing
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
Caucasian	germline	yes	2	not provided	not provided	not provided	not provided	clinical testing
Caucasian Non Hispanic	germline	yes	2	not provided	not provided	not provided	not provided	clinical testing
Causasians	germline	yes	not provided	1	not provided	not provided	yes	clinical testing
Central/Eastern European	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
English, Scottish, French	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Welsh, English	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Western European	germline	yes	16	not provided	not provided	not provided	not provided	clinical testing
Western European, Caucasian, Adopted	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Variation in breast cancer risk associated with factors related to pregnancies according to truncating mutation location, in the French National BRCA1 and BRCA2 mutations carrier cohort (GENEPSO).

Lecarpentier J, Noguès C, Mouret-Fourme E, Gauthier-Villars M, Lasset C, Fricker JP, Caron O, Stoppa-Lyonnet D, Berthet P, Faivre L, Bonadona V, Buecher B, Coupier I, Gladieff L, Gesta P, Eisinger F, Frénay M, Luporsi E, Lortholary A, Colas C, Dugast C, Longy M, et al.

Breast Cancer Res. 2012 Jul 3;14(4):R99. doi: 10.1186/bcr3218.

PubMed [citation]

PMID:: 22762150
PMCID:: PMC3680948

Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis of EMBRACE.

Mavaddat N, Peock S, Frost D, Ellis S, Platte R, Fineberg E, Evans DG, Izatt L, Eeles RA, Adlard J, Davidson R, Eccles D, Cole T, Cook J, Brewer C, Tischkowitz M, Douglas F, Hodgson S, Walker L, Porteous ME, Morrison PJ, Side LE, et al.

J Natl Cancer Inst. 2013 Jun 5;105(11):812-22. doi: 10.1093/jnci/djt095. Epub 2013 Apr 29.

PubMed [citation]

PMID:: 23628597

See all PubMed Citations (19)

Details of each submission

From Sharing Clinical Reports Project (SCRP), SCV000054271.6

#	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	30	not provided	not provided		not provided	not provided	not provided	not provided

From Breast Cancer Information Core (BIC) (BRCA2), SCV000147015.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	7	not provided	not provided	clinical testing	not provided
2	Caucasian	1	not provided	not provided	clinical testing	not provided
3	Caucasian	1	not provided	not provided	clinical testing	not provided
4	Caucasian Non Hispanic	2	not provided	not provided	clinical testing	not provided
5	Central/Eastern European	1	not provided	not provided	clinical testing	not provided
6	English, Scottish, French	1	not provided	not provided	clinical testing	not provided
7	Welsh, English	1	not provided	not provided	clinical testing	not provided
8	Western European	16	not provided	not provided	clinical testing	not provided
9	Western European, Caucasian, Adopted	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		7	not provided	not provided	not provided
2	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
3	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
4	germline	yes	not provided	not provided	not provided		2	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		1	not provided	not provided	not provided
7	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
8	germline	yes	not provided	not provided	not provided		16	not provided	not provided	not provided
9	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Michigan Medical Genetics Laboratories, University of Michigan, SCV000196001.1

#	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	germline	yes	not provided	Blood	not provided		not provided	not provided	not provided	not provided

From Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA), SCV000282439.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided

Description

Variant allele predicted to encode a truncated non-functional protein.

#	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 Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge, SCV000327588.4

#	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	99	not provided

From Counsyl, SCV000488257.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

#	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 Genologica Medica, SCV000577969.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Causasians	not provided	not provided	yes	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	Blood	not provided		not provided	not provided	1	not provided

From Department of Medical Genetics, Oslo University Hospital, SCV000605676.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	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		3	not provided	not provided	not provided

From Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus, SCV000733293.1

#	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, SCV000744510.1

#	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 Geisinger Autism and Developmental Medicine Institute, Geisinger Health System, SCV000804428.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	provider interpretation	PubMed (7)
2	not provided	1	not provided	not provided	clinical testing	PubMed (7)

Description

This 6 year old male with global developmental delays (at-risk for mild intellectual disability), ADHD, disruptive behavior, and mild overgrowth was found to carry a maternally inherited 2 bp deletion in the BRCA2 gene. The c.7069_7070delCT pathogenic variant in the BRCA2 gene, previously reported as 7297delCT using alternate nomenclature, has been published in association with early-onset breast cancer, ovarian cancer, and prostate cancer (Garvin et al., 1997; Zhang et al., 2011; Cunningham et al., 2014; Song et al., 2014; Ellingson et al., 2015; Decker et al., 2016). The deletion causes a frameshift and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Given that this is an adult-onset condition, the patient is not expected to be affected at this time. The patient's mother has not been formally evaluated in the oncology setting, so her current status is unknown.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	maternal	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided
2	maternal	no	1	not provided	not provided		1	not provided	not provided	not provided

From Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine, SCV001434856.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This c.7069_7070delCT (p.Leu2357Valfs*2) frameshift variant in the BRCA2 gene is predicted to introduce a premature translation termination codon. It has been reported in multiple unrelated patients and families affected with breast cancer [PMID 9429140, 18465347, 21120943, 21324516, 24504028] and is extremely rare in general population. Therefore, this variant in the BRCA2 gene is 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 Genetics and Molecular Pathology, SA Pathology, SCV002761530.1

#	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	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Institute of Human Genetics, University of Leipzig Medical Center, SCV004100706.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

Criteria applied: PVS1,PS4,PM5_STR

#	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, SCV004243752.1

#	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 All of Us Research Program, National Institutes of Health, SCV004844359.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	5	not provided	not provided	clinical testing	PubMed (12)

Description

This variant deletes 2 nucleotides in exon 14 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is also known as 7297delCT in the literature according to the BIC nomenclature. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in over ten individuals affected with breast and/or ovarian cancer (PMID: 9667259, 16234499, 18824701, 20104584, 21324516, 21913181, 24504028, 24549055, 24728189), as well as colorectal cancer (PMID: 27978560) and high grade prostate cancer (PMID: 34700141). This variant has been identified in 7/282332 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		5	not provided	not provided	not provided

From Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, SCV005045980.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

PVS1; PM5_PTC_Strong

#	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 Baylor Genetics, SCV005049484.1

#	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

Last Updated: Nov 3, 2024

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