NM_000059.4(BRCA2):c.3856A>G (p.Lys1286Glu) AND Hereditary breast ovarian cancer syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 17, 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:: RCV001295751.6

Allele description [Variation Report for NM_000059.4(BRCA2):c.3856A>G (p.Lys1286Glu)]

NM_000059.4(BRCA2):c.3856A>G (p.Lys1286Glu)

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.3856A>G (p.Lys1286Glu)

HGVS:

NC_000013.11:g.32338211A>G
NG_012772.3:g.27732A>G
NM_000059.4:c.3856A>GMANE SELECT
NP_000050.2:p.Lys1286Glu
NP_000050.3:p.Lys1286Glu
LRG_293t1:c.3856A>G
LRG_293:g.27732A>G
LRG_293p1:p.Lys1286Glu
NC_000013.10:g.32912348A>G
NM_000059.3:c.3856A>G
U43746.1:n.4084A>G

Protein change:

K1286E

Links:

dbSNP: rs80358629

NCBI 1000 Genomes Browser:

rs80358629

Molecular consequence:

NM_000059.4:c.3856A>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001484696	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 17, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 12955716, 9761393, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001484696

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 17, 2019)

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

Analysis of BRCA1 and BRCA2 genes in Spanish breast/ovarian cancer patients: a high proportion of mutations unique to Spain and evidence of founder effects.

Díez O, Osorio A, Durán M, Martinez-Ferrandis JI, de la Hoya M, Salazar R, Vega A, Campos B, Rodríguez-López R, Velasco E, Chaves J, Díaz-Rubio E, Jesús Cruz J, Torres M, Esteban E, Cervantes A, Alonso C, San Román JM, González-Sarmiento R, Miner C, Carracedo A, Eugenia Armengod M, et al.

Hum Mutat. 2003 Oct;22(4):301-12.

PubMed [citation]

PMID:: 12955716

Molecular analysis of the BRCA2 gene in 16 breast/ovarian cancer Spanish families.

Osorio A, Robledo M, Martínez B, Cebrián A, San Román JM, Albertos J, Lobo F, Benítez J.

Clin Genet. 1998 Aug;54(2):142-7.

PubMed [citation]

PMID:: 9761393

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001484696.3

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

Description

This variant has been observed in several individuals affected with breast and/or ovarian cancer, as well as in unaffected individuals (PMID: 12955716, 9761393). ClinVar contains an entry for this variant (Variation ID: 51542). This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with glutamic acid at codon 1286 of the BRCA2 protein (p.Lys1286Glu). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and glutamic acid. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain.

#	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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