NM_000059.4(BRCA2):c.516+2T>A AND Hereditary breast ovarian cancer syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 12, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001387342.13

Allele description [Variation Report for NM_000059.4(BRCA2):c.516+2T>A]

NM_000059.4(BRCA2):c.516+2T>A

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.516+2T>A

HGVS:

NC_000013.11:g.32326284T>A
NG_012772.3:g.15805T>A
NM_000059.4:c.516+2T>AMANE SELECT
NM_001406719.1:c.516+2T>A
NM_001406720.1:c.516+2T>A
NM_001406721.1:c.516+2T>A
NM_001406722.1:c.147+2T>A
LRG_293t1:c.516+2T>A
LRG_293:g.15805T>A
NC_000013.10:g.32900421T>A
NM_000059.3:c.516+2T>A

Links:

dbSNP: rs397507764

NCBI 1000 Genomes Browser:

rs397507764

Molecular consequence:

NM_000059.4:c.516+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406719.1:c.516+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406720.1:c.516+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406721.1:c.516+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406722.1:c.147+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Hereditary breast ovarian cancer syndrome
Synonyms:: Hereditary breast and ovarian cancer syndrome; Hereditary breast and ovarian cancer; Hereditary breast and ovarian cancer syndrome (HBOC); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0003582; MeSH: D061325; MedGen: C0677776; Orphanet: 145

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LPS-induced systemic inflammation is suppressed by the PDZ motif peptide of ZO-1...
LPS-induced systemic inflammation is suppressed by the PDZ motif peptide of ZO-1 via regulation of macrophage M1/M2 polarization
LPS-induced systemic inflammation is suppressed by the PDZ motif peptide of ZO-1 via regulation of macrophage M1/M2 polarization

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001587949	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 12, 2019)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 16199547, 20104584, 31343793, 11802209, 29446198, 27886673, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001587949

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 12, 2019)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study.

Borg A, Haile RW, Malone KE, Capanu M, Diep A, Törngren T, Teraoka S, Begg CB, Thomas DC, Concannon P, Mellemkjaer L, Bernstein L, Tellhed L, Xue S, Olson ER, Liang X, Dolle J, Børresen-Dale AL, Bernstein JL.

Hum Mutat. 2010 Mar;31(3):E1200-40. doi: 10.1002/humu.21202.

PubMed [citation]

PMID:: 20104584
PMCID:: PMC2928257

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001587949.4

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

Description

For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 31343793). This variant has been observed in individual(s) with clinical features of hereditary breast and ovarian cancer syndrome (PMID: 11802209, 29446198, 27886673). This variant is also known as IVS6+2T>A in the literature. ClinVar contains an entry for this variant (Variation ID: 51789). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 6 of the BRCA2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.

#	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

Last Updated: Sep 29, 2024

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Relating variation to medicine