NM_000059.4(BRCA2):c.7806-2A>G AND not provided

Germline classification:: Pathogenic (6 submissions)
Last evaluated:: May 15, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001281729.30

Allele description [Variation Report for NM_000059.4(BRCA2):c.7806-2A>G]

NM_000059.4(BRCA2):c.7806-2A>G

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.7806-2A>G

HGVS:

NC_000013.11:g.32362521A>G
NG_012772.3:g.52042A>G
NM_000059.4:c.7806-2A>GMANE SELECT
NM_001406719.1:c.7710-2A>G
NM_001406720.1:c.7806-2A>G
NM_001406721.1:c.2874-2A>G
NM_001406722.1:c.1389-2A>G
LRG_293t1:c.7806-2A>G
LRG_293:g.52042A>G
NC_000013.10:g.32936658A>G
NM_000059.3:c.7806-2A>G
U43746.1:n.8034-2A>G

Nucleotide change:

IVS16-2A>G

Links:

Breast Cancer Information Core (BIC) (BRCA2): 8034-2&base_change=A to G; dbSNP: rs81002836

NCBI 1000 Genomes Browser:

rs81002836

Molecular consequence:

NM_000059.4:c.7806-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406719.1:c.7710-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406720.1:c.7806-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406721.1:c.2874-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406722.1:c.1389-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

SRP290277 (14)
SRA

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000296681	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Jan 29, 2020)	unknown	clinical testing	PubMed (10) [See all records that cite these PMIDs] 10449599, 28339459, 29446198, 12461697, 22505045, 22923021, 21232165, 24312913, 26467025, 26295337
SCV001927448	Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001959599	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV002097424	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Feb 2, 2022)	germline	clinical testing	Citation Link,
SCV002563165	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Dec 1, 2020)	germline	clinical testing	Citation Link,
SCV005199824	Clinical Genetics Laboratory, Skane University Hospital Lund	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 15, 2023)	germline	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	1	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

Citations

PubMed

BRCA1 and BRCA2 genes: role in hereditary breast and ovarian cancer in Italy.

Santarosa M, Dolcetti R, Magri MD, Crivellari D, Tibiletti MG, Gallo A, Tumolo S, Della Puppa L, Furlan D, Boiocchi M, Viel A.

Int J Cancer. 1999 Sep 24;83(1):5-9.

PubMed [citation]

PMID:: 10449599

Functional classification of DNA variants by hybrid minigenes: Identification of 30 spliceogenic variants of BRCA2 exons 17 and 18.

Fraile-Bethencourt E, Díez-Gómez B, Velásquez-Zapata V, Acedo A, Sanz DJ, Velasco EA.

PLoS Genet. 2017 Mar;13(3):e1006691. doi: 10.1371/journal.pgen.1006691.

PubMed [citation]

PMID:: 28339459
PMCID:: PMC5384790

See all PubMed Citations (11)

Details of each submission

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000296681.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

Description

This variant is located in a canonical splice-acceptor site and interferes with normal BRCA2 mRNA splicing. In the published literature, this variant has been reported in individuals with hereditary breast and/or ovarian cancer (PMID: 29446198 (2018), 10449599 (1999)). Additionally, it has been described as a founder variant in Slovenian breast cancer populations (PMID: 24312913 (2013), PMID: 21232165 (2011), 12461697 (2002)). Functional studies have confirmed that this variant leads to aberrant splicing (PMID: 28339459 (2017), 10449599 (1999)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as pathogenic.

#	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 Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus, SCV001927448.1

#	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 Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001959599.1

#	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 GeneDx, SCV002097424.2

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

Description

Canonical splice site variant the produces multiple transcripts, leading to an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product (Santarosa 1999, Krajc 2002, Fraile-Bethencourt 2017, Gelli 2019); Observed in individuals with a personal or family history consistent with pathogenic variants in this gene, and is a founder variant in the Slovenian and North-Eastern Italian populations (Santarosa 1999, Krajc 2002, Marroni 2004, Besic 2008, Stegel 2011, Cini 2016); Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 8034-2A>G; This variant is associated with the following publications: (PMID: 19818148, 20104584, 26295337, 29907814, 12461697, 15340362, 22505045, 22923021, 25525159, 10449599, 10923033, 28339459, 24156927, 26852130, 22984553, 17301269, 16764716, 21232165, 18439106, 18783588, 23397983, 12097290, 24312913, 23199084, 25186627, 29470806, 29446198, 34399810, 33891299, 31131967, 12228710, 30832263, 30613976, 31360904)

#	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 CeGaT Center for Human Genetics Tuebingen, SCV002563165.16

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

From Clinical Genetics Laboratory, Skane University Hospital Lund, SCV005199824.1

#	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

Last Updated: Oct 26, 2024

ClinVar

Relating variation to medicine