NM_000059.3(BRCA2):c.5583dupA (p.Val1862Serfs) AND Hereditary breast and ovarian cancer syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 1, 2017
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:: RCV000044687.5

Allele description

NM_000059.3(BRCA2):c.5583dupA (p.Val1862Serfs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.3(BRCA2):c.5583dupA (p.Val1862Serfs)

HGVS:

NC_000013.11:g.32339938dupA
NG_012772.3:g.29459dup
NM_000059.3:c.5583dupA
NP_000050.2:p.Val1862Serfs
LRG_293t1:c.5583dupA
LRG_293:g.29459dup
LRG_293p1:p.Val1862Serfs
NC_000013.10:g.32914075dupA
NM_000059.3:c.5583dup
p.K1861KFS*12

Links:

dbSNP: rs397507790

NCBI 1000 Genomes Browser:

rs397507790

Molecular consequence:

NM_000059.3:c.5583dupA - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hereditary breast and ovarian cancer syndrome (HBOC)
Synonyms:: Hereditary breast and ovarian cancer
Identifiers:: MeSH: D061325; MedGen: C0677776; Orphanet: 145; OMIM: PS604370

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000072700	Invitae	criteria provided, single submitter (Nykamp K et al. (Genet Med 2017))	Pathogenic (Sep 1, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22762150, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000072700

Invitae

criteria provided, single submitter

(Nykamp K et al. (Genet Med 2017))

Pathogenic
(Sep 1, 2017)

germline

clinical testing

PubMed (2)
[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

Variation in breast cancer risk associated with factors related to pregnancies according to truncating mutation location, in the French National BRCA1 and BRCA2 mutations carrier cohort (GENEPSO).

Lecarpentier J, Noguès C, Mouret-Fourme E, Gauthier-Villars M, Lasset C, Fricker JP, Caron O, Stoppa-Lyonnet D, Berthet P, Faivre L, Bonadona V, Buecher B, Coupier I, Gladieff L, Gesta P, Eisinger F, Frénay M, Luporsi E, Lortholary A, Colas C, Dugast C, Longy M, et al.

Breast Cancer Res. 2012 Jul 3;14(4):R99. doi: 10.1186/bcr3218.

PubMed [citation]

PMID:: 22762150
PMCID:: PMC3680948

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9..

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000072700.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change inserts 1 nucleotide in exon 11 of the BRCA2 mRNA (c.5583dupA), causing a frameshift at codon 1862. This creates a premature translational stop signal (p.Val1862Serfs*11) and is expected to result in an absent or disrupted protein product. Truncating variants in BRCA2 are known to be pathogenic. This particular truncation has been reported in the literature in an individual from a family affected with breast cancer (PMID: 22762150). This variant is also known as c.5582dup in the literature. 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: Sep 30, 2018

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