NM_000059.4(BRCA2):c.518_631+462delinsAAAGAAATTTTATTTCTTT AND Hereditary breast ovarian cancer syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 6, 2023
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:: RCV003531300.2

Allele description [Variation Report for NM_000059.4(BRCA2):c.518_631+462delinsAAAGAAATTTTATTTCTTT]

NM_000059.4(BRCA2):c.518_631+462delinsAAAGAAATTTTATTTCTTT

Gene:

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

Variant type:

Indel

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.518_631+462delinsAAAGAAATTTTATTTCTTT

HGVS:

NC_000013.11:g.32326500_32327075delinsAAAGAAATTTTATTTCTTT
NG_012772.3:g.16021_16596delinsAAAGAAATTTTATTTCTTT
NM_000059.4:c.518_631+462delinsAAAGAAATTTTATTTCTTTMANE SELECT
NM_001406719.1:c.518_631+462delinsAAAGAAATTTTATTTCTTT
NM_001406720.1:c.518_631+462delinsAAAGAAATTTTATTTCTTT
NM_001406721.1:c.518_631+462delinsAAAGAAATTTTATTTCTTT
NM_001406722.1:c.149_262+462delinsAAAGAAATTTTATTTCTTT
LRG_293:g.16021_16596delinsAAAGAAATTTTATTTCTTT
NC_000013.10:g.32900637_32901212delinsAAAGAAATTTTATTTCTTT

Molecular consequence:

NM_000059.4:c.518_631+462delinsAAAGAAATTTTATTTCTTT - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406719.1:c.518_631+462delinsAAAGAAATTTTATTTCTTT - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406720.1:c.518_631+462delinsAAAGAAATTTTATTTCTTT - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406721.1:c.518_631+462delinsAAAGAAATTTTATTTCTTT - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406722.1:c.149_262+462delinsAAAGAAATTTTATTTCTTT - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004320940	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Sep 6, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16199547, 20104584, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004320940

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Sep 6, 2023)

germline

clinical testing

PubMed (3)
[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 (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004320940.1

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

Description

This variant results in the deletion of part of exon 7 (c.518_631+462delins19) of the BRCA2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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

Last Updated: Sep 29, 2024

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