NM_000059.4(BRCA2):c.3860dup (p.Asn1287fs) AND Hereditary breast ovarian cancer syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 27, 2024
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:: RCV000496333.16

Allele description [Variation Report for NM_000059.4(BRCA2):c.3860dup (p.Asn1287fs)]

NM_000059.4(BRCA2):c.3860dup (p.Asn1287fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.3860dup (p.Asn1287fs)

Other names:

4088insA

HGVS:

NC_000013.11:g.32338215dup
NG_012772.3:g.27736dup
NM_000059.4:c.3860dupMANE SELECT
NM_000059.4:c.3860dupA
NP_000050.3:p.Asn1287fs
LRG_293t1:c.3860dup
LRG_293:g.27736dup
NC_000013.10:g.32912345_32912346insA
NC_000013.10:g.32912352dup
NM_000059.3:c.3860dup
NM_000059.3:c.3860dupA
NM_000059.4:c.3860dup
U43746.1:n.4088_4089insA
p.N1287KfsX2

Protein change:

N1287fs

Links:

Breast Cancer Information Core (BIC) (BRCA2): 4088&base_change=ins A; dbSNP: rs80359406

NCBI 1000 Genomes Browser:

rs80359406

Molecular consequence:

NM_000059.4:c.3860dup - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000587684	Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto - The Canadian Open Genetics Repository (COGR)	no assertion criteria provided	Pathogenic (Jan 31, 2014)	germline	research
SCV001577950	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 27, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 20104584, 11039575, 18214034, 29446198, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000587684

Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto - The Canadian Open Genetics Repository (COGR)

no assertion criteria provided

Pathogenic
(Jan 31, 2014)

germline

research

SCV001577950

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 27, 2024)

germline

clinical testing

PubMed (5)
[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	yes	not provided	not provided	not provided	not provided	not provided	research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Multiple founder effects and geographical clustering of BRCA1 and BRCA2 families in Finland.

Sarantaus L, Huusko P, Eerola H, Launonen V, Vehmanen P, Rapakko K, Gillanders E, Syrjäkoski K, Kainu T, Vahteristo P, Krahe R, Pääkkönen K, Hartikainen J, Blomqvist C, Löppönen T, Holli K, Ryynänen M, Bützow R, Borg A, Wasteson Arver B, Holmberg E, Mannermaa A, et al.

Eur J Hum Genet. 2000 Oct;8(10):757-63.

PubMed [citation]

PMID:: 11039575

See all PubMed Citations (5)

Details of each submission

From Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto - The Canadian Open Genetics Repository (COGR), SCV000587684.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001577950.4

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

Description

This sequence change creates a premature translational stop signal (p.Asn1287Lysfs*2) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. 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 premature translational stop signal has been observed in individual(s) with or at high risk of breast and/or ovarian cancer and hereditary breast and ovarian cancer (HBOC) (PMID: 11039575, 18214034, 29446198). It has also been observed to segregate with disease in related individuals. This variant is also known as 4081insA or 4088insA. ClinVar contains an entry for this variant (Variation ID: 51546). For these reasons, this variant has been 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

Last Updated: Nov 3, 2024

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