NM_000059.4(BRCA2):c.156_157insGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACGAGGTCAGGAG (p.Lys53delinsAlaGlyArgGlyGlySerArgLeuTer) AND Hereditary breast ovarian cancer syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 11, 2018
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:: RCV001939565.6

Allele description [Variation Report for NM_000059.4(BRCA2):c.156_157insGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACGAGGTCAGGAG (p.Lys53delinsAlaGlyArgGlyGlySerArgLeuTer)]

NM_000059.4(BRCA2):c.156_157insGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACGAGGTCAGGAG (p.Lys53delinsAlaGlyArgGlyGlySerArgLeuTer)

Gene:

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

Variant type:

Insertion

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.156_157insGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACGAGGTCAGGAG (p.Lys53delinsAlaGlyArgGlyGlySerArgLeuTer)

HGVS:

NC_000013.11:g.32319165_32319166insGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACGAGGTCAGGAG
NG_012772.3:g.8686_8687insGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACGAGGTCAGGAG
NG_017006.2:g.1198_1199insCTCCTGACCTCGTGATCCGCCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGC
NM_000059.4:c.156_157insGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACGAGGTCAGGAGMANE SELECT
NP_000050.3:p.Lys53delinsAlaGlyArgGlyGlySerArgLeuTer
LRG_293:g.8686_8687insGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACGAGGTCAGGAG
NC_000013.10:g.32893302_32893303insGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACGAGGTCAGGAG

Links:

dbSNP: rs1593882502

NCBI 1000 Genomes Browser:

rs1593882502

Molecular consequence:

NM_000059.4:c.156_157insGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACGAGGTCAGGAG - nonsense - [Sequence Ontology: SO:0001587]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002235072	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 11, 2018)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 16088935, 9126734, 10980621, 17513806, 18363094, 20652400, 22829013, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002235072

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 11, 2018)

germline

clinical testing

PubMed (8)
[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

De novo Alu element insertions targeted to a sequence common to the BRCA1 and BRCA2 genes.

Teugels E, De Brakeleer S, Goelen G, Lissens W, Sermijn E, De Grève J.

Hum Mutat. 2005 Sep;26(3):284.

PubMed [citation]

PMID:: 16088935

Transcriptional activation functions in BRCA2.

Milner J, Ponder B, Hughes-Davies L, Seltmann M, Kouzarides T.

Nature. 1997 Apr 24;386(6627):772-3. No abstract available.

PubMed [citation]

PMID:: 9126734

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002235072.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This sequence change is an Alu-mediated insertion in exon 3 of the BRCA2 mRNA (c.156_157insAlu). Experimental studies have shown that this insertion causes alternative splicing of BRCA2, leading to an in-frame skipping of exon 3 (PMID: 18363094, 16088935). For these reasons, this variant has been classified as Pathogenic. Exon 3 contains two transcription-activating regions, and is required for BRCA2 phosphorylation (PMID: 9126734, 10980621). Loss-of-function variants in BRCA2 are known to be pathogenic. This particular variant is clearly defined as a breast and/or ovarian cancer causative allele and is a common cause of cancer in individuals of Portuguese ancestry (PMID: 17513806, 18363094, 20652400, 22829013).

#	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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